rs201688836
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Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2
The NM_001148.6(ANK2):āc.7251T>Cā(p.Asp2417=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00015 ( 0 hom., cov: 32)
Exomes š: 0.00017 ( 0 hom. )
Consequence
ANK2
NM_001148.6 synonymous
NM_001148.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.928
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -17 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 4-113355869-T-C is Benign according to our data. Variant chr4-113355869-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 413958.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.928 with no splicing effect.
BS2
?
High AC in GnomAd4 at 23 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ANK2 | NM_001148.6 | c.7251T>C | p.Asp2417= | synonymous_variant | 38/46 | ENST00000357077.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ANK2 | ENST00000357077.9 | c.7251T>C | p.Asp2417= | synonymous_variant | 38/46 | 1 | NM_001148.6 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.000151 AC: 23AN: 152096Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000283 AC: 71AN: 250792Hom.: 0 AF XY: 0.000317 AC XY: 43AN XY: 135504
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GnomAD4 exome AF: 0.000172 AC: 252AN: 1461812Hom.: 0 Cov.: 35 AF XY: 0.000169 AC XY: 123AN XY: 727202
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GnomAD4 genome ? AF: 0.000151 AC: 23AN: 152096Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74310
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 08, 2021 | - - |
Long QT syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 15, 2019 | 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
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Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at