rs35956627
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001148.6(ANK2):āc.2970A>Cā(p.Arg990=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000549 in 1,614,208 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0031 ( 4 hom., cov: 33)
Exomes š: 0.00029 ( 3 hom. )
Consequence
ANK2
NM_001148.6 synonymous
NM_001148.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.55
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
?
Variant 4-113330315-A-C is Benign according to our data. Variant chr4-113330315-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 190527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113330315-A-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=-1.55 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00306 (466/152342) while in subpopulation AFR AF= 0.0109 (453/41578). AF 95% confidence interval is 0.0101. There are 4 homozygotes in gnomad4. There are 223 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 466 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANK2 | NM_001148.6 | c.2970A>C | p.Arg990= | synonymous_variant | 27/46 | ENST00000357077.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK2 | ENST00000357077.9 | c.2970A>C | p.Arg990= | synonymous_variant | 27/46 | 1 | NM_001148.6 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00306 AC: 466AN: 152224Hom.: 4 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
466
AN:
152224
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000832 AC: 209AN: 251310Hom.: 4 AF XY: 0.000523 AC XY: 71AN XY: 135826
GnomAD3 exomes
AF:
AC:
209
AN:
251310
Hom.:
AF XY:
AC XY:
71
AN XY:
135826
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000288 AC: 421AN: 1461866Hom.: 3 Cov.: 31 AF XY: 0.000252 AC XY: 183AN XY: 727230
GnomAD4 exome
AF:
AC:
421
AN:
1461866
Hom.:
Cov.:
31
AF XY:
AC XY:
183
AN XY:
727230
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00306 AC: 466AN: 152342Hom.: 4 Cov.: 33 AF XY: 0.00299 AC XY: 223AN XY: 74508
GnomAD4 genome
?
AF:
AC:
466
AN:
152342
Hom.:
Cov.:
33
AF XY:
AC XY:
223
AN XY:
74508
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1
AN:
3478
ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Long QT syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 15, 2024 | - - |
Cardiac arrhythmia, ankyrin-B-related Benign:2
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Dec 05, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jul 28, 2021 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 16, 2014 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | ANK2: BP4, BP7, BS1, BS2 - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 01, 2016 | This alteration is classified as 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:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at