rs145895389

Variant names:

• chr4-113356972-C-T
• rs145895389
• NM_001148.6:c.8354C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001148.6(ANK2):​c.8354C>T​(p.Ser2785Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00227 in 1,613,964 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (8 hom.)
• Consequence: ANK2 NM_001148.6 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.589
• Publications: 7 publications found

Genes affected

ANK2 (HGNC:493): (ankyrin 2) This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]

ANK2 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, ClinGen
• Brugada syndrome

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Genomics England PanelApp, ClinGen
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: ClinGen, Genomics England PanelApp
• heart conduction disease

  Inheritance: AD Classification: LIMITED Submitted by: Genomics England PanelApp
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: G2P
• cardiac arrhythmia, ankyrin-B-related

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• long QT syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0053032637).
• BP6: Variant 4-113356972-C-T is Benign according to our data. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113356972-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 191540.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00163 (248/152278) while in subpopulation NFE AF = 0.00309 (210/68006). AF 95% confidence interval is 0.00275. There are 0 homozygotes in GnomAd4. There are 109 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 248 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ANK2	NM_001148.6	c.8354C>T	p.Ser2785Leu	missense_variant	Exon 38 of 46	ENST00000357077.9	NP_001139.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ANK2	ENST00000357077.9	c.8354C>T	p.Ser2785Leu	missense_variant	Exon 38 of 46	1	NM_001148.6	ENSP00000349588.4

Frequencies

GnomAD3 genomes AF: 0.00163 AC: 248 AN: 152160 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00309

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00161 AC: 402 AN: 250120 AF XY: 0.00161

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00119

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000878

Gnomad NFE exome AF: 0.00302

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.00234 AC: 3416 AN: 1461686 Hom.: 8 Cov.: 35 AF XY: 0.00228 AC XY: 1659 AN XY: 727152

African (AFR) AF: 0.000359 AC: 12 AN: 33472

American (AMR) AF: 0.000492 AC: 22 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00145 AC: 38 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86256

European-Finnish (FIN) AF: 0.00107 AC: 57 AN: 53406

Middle Eastern (MID) AF: 0.000867 AC: 5 AN: 5766

European-Non Finnish (NFE) AF: 0.00280 AC: 3115 AN: 1111866

Other (OTH) AF: 0.00257 AC: 155 AN: 60384

GnomAD4 genome AF: 0.00163 AC: 248 AN: 152278 Hom.: 0 Cov.: 32 AF XY: 0.00146 AC XY: 109 AN XY: 74456

African (AFR) AF: 0.000409 AC: 17 AN: 41572

American (AMR) AF: 0.000458 AC: 7 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00309 AC: 210 AN: 68006

Other (OTH) AF: 0.00142 AC: 3 AN: 2110

Alfa AF: 0.00229 Hom.: 2

Bravo AF: 0.00143

TwinsUK AF: 0.00243 AC: 9

ALSPAC AF: 0.00311 AC: 12

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00221 AC: 19

ExAC AF: 0.00186 AC: 226

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

-

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 28, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:3

Jun 15, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 24, 2013

Biesecker Lab/Clinical Genomics Section, National Institutes of Health

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: research

- -

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ANK2: BP4, BS1 -

Cardiac arrhythmia, ankyrin-B-related Benign:3

Oct 09, 2014

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

ANK2-related disorder Benign:1

Jun 07, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Long QT syndrome Benign:1

Jan 26, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype Benign:1

Nov 28, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.073
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	6.8
DANN	Benign	0.064
DEOGEN2	Benign	0.30	T;T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.73
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.83	T;T;T
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.0053	T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Uncertain	2.1	M;.;.
PhyloP100		0.59
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.65	N;N;.
REVEL	Benign	0.051
Sift	Benign	0.25	T;T;.
Sift4G	Benign	0.12	T;T;D
Vest4		0.055
MVP		0.40
MPC		0.071
ClinPred		0.0043	T
GERP RS		3.7
Varity_R		0.076
gMVP		0.018
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs145895389; hg19: chr4-114278128;