rs2272230

Positions:

• chr4-113339382-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001148.6(ANK2):​c.3893+60C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.12 in 1,337,118 control chromosomes in the GnomAD database, including 14,857 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.20 (5200 hom., cov: 32)
  • Exomes 𝑓: 0.11 (9657 hom.)
• Consequence: ANK2 NM_001148.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.226

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 4-113339382-C-T is Benign according to our data. Variant chr4-113339382-C-T is described in ClinVar as [Benign]. Clinvar id is 1229699.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ANK2	NM_001148.6	c.3893+60C>T		intron_variant		ENST00000357077.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ANK2	ENST00000357077.9	c.3893+60C>T		intron_variant		1	NM_001148.6	A2

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30915 AN: 151928 Hom.: 5176 Cov.: 32

Gnomad AFR AF: 0.463

Gnomad AMI AF: 0.0341

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.0971

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0627

Gnomad MID AF: 0.133

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.109 AC: 129364 AN: 1185072 Hom.: 9657 AF XY: 0.109 AC XY: 65767 AN XY: 603062

Gnomad4 AFR exome AF: 0.472

Gnomad4 AMR exome AF: 0.137

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.124

Gnomad4 SAS exome AF: 0.125

Gnomad4 FIN exome AF: 0.0659

Gnomad4 NFE exome AF: 0.0955

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.204 AC: 30983 AN: 152046 Hom.: 5200 Cov.: 32 AF XY: 0.199 AC XY: 14768 AN XY: 74334

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.0971

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.119

Gnomad4 FIN AF: 0.0627

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.181

Alfa AF: 0.114 Hom.: 1975

Bravo AF: 0.222

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.48
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2272230; hg19: chr4-114260538;