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NM_001148.6(ANK2):c.1937C>T (p.Ser646Phe) AND ANK2-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 27, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003398876.4

Allele description [Variation Report for NM_001148.6(ANK2):c.1937C>T (p.Ser646Phe)]

NM_001148.6(ANK2):c.1937C>T (p.Ser646Phe)

Gene:
ANK2:ankyrin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
4q26
Genomic location:
Preferred name:
NM_001148.6(ANK2):c.1937C>T (p.Ser646Phe)
Other names:
p.S646F:TCC>TTC
HGVS:
  • NC_000004.12:g.113282730C>T
  • NG_009006.2:g.469648C>T
  • NM_001127493.3:c.1874C>T
  • NM_001148.6:c.1937C>TMANE SELECT
  • NM_001354225.2:c.1937C>T
  • NM_001354228.2:c.1937C>T
  • NM_001354230.2:c.1982C>T
  • NM_001354231.2:c.1982C>T
  • NM_001354232.2:c.1937C>T
  • NM_001354235.2:c.1937C>T
  • NM_001354236.2:c.1937C>T
  • NM_001354237.2:c.1982C>T
  • NM_001354239.2:c.1874C>T
  • NM_001354240.2:c.1982C>T
  • NM_001354241.2:c.1982C>T
  • NM_001354242.2:c.1982C>T
  • NM_001354243.2:c.1874C>T
  • NM_001354244.2:c.1874C>T
  • NM_001354245.2:c.1838C>T
  • NM_001354246.2:c.1937C>T
  • NM_001354249.2:c.1850C>T
  • NM_001354252.2:c.1874C>T
  • NM_001354253.2:c.1775C>T
  • NM_001354254.2:c.1874C>T
  • NM_001354255.2:c.1874C>T
  • NM_001354256.2:c.1874C>T
  • NM_001354257.2:c.1775C>T
  • NM_001354258.2:c.1937C>T
  • NM_001354260.2:c.1751C>T
  • NM_001354261.2:c.1895C>T
  • NM_001354262.2:c.1874C>T
  • NM_001354264.2:c.1850C>T
  • NM_001354265.2:c.1937C>T
  • NM_001354266.2:c.1850C>T
  • NM_001354267.2:c.1850C>T
  • NM_001354268.2:c.1838C>T
  • NM_001354269.3:c.1727C>T
  • NM_001354270.2:c.1775C>T
  • NM_001354271.2:c.1751C>T
  • NM_001354272.2:c.1874C>T
  • NM_001354273.2:c.1739C>T
  • NM_001354274.2:c.1850C>T
  • NM_001354275.2:c.1874C>T
  • NM_001354276.2:c.1850C>T
  • NM_001354277.2:c.1652C>T
  • NM_001386142.1:c.1850C>T
  • NM_001386143.1:c.1874C>T
  • NM_001386144.1:c.1982C>T
  • NM_001386146.1:c.1850C>T
  • NM_001386147.1:c.1895C>T
  • NM_001386148.2:c.1925C>T
  • NM_001386149.1:c.1850C>T
  • NM_001386150.1:c.1850C>T
  • NM_001386151.1:c.1751C>T
  • NM_001386152.1:c.1982C>T
  • NM_001386153.1:c.1850C>T
  • NM_001386154.1:c.1850C>T
  • NM_001386156.1:c.1775C>T
  • NM_001386157.1:c.1652C>T
  • NM_001386158.1:c.1553C>T
  • NM_001386160.1:c.1895C>T
  • NM_001386161.1:c.1874C>T
  • NM_001386162.1:c.1850C>T
  • NM_001386174.1:c.1988C>T
  • NM_001386175.1:c.1964C>T
  • NM_001386186.2:c.1925C>T
  • NM_001386187.2:c.1901C>T
  • NM_020977.5:c.1937C>T
  • NP_001120965.1:p.Ser625Phe
  • NP_001139.3:p.Ser646Phe
  • NP_001341154.1:p.Ser646Phe
  • NP_001341157.1:p.Ser646Phe
  • NP_001341159.1:p.Ser661Phe
  • NP_001341160.1:p.Ser661Phe
  • NP_001341161.1:p.Ser646Phe
  • NP_001341164.1:p.Ser646Phe
  • NP_001341165.1:p.Ser646Phe
  • NP_001341166.1:p.Ser661Phe
  • NP_001341168.1:p.Ser625Phe
  • NP_001341169.1:p.Ser661Phe
  • NP_001341170.1:p.Ser661Phe
  • NP_001341171.1:p.Ser661Phe
  • NP_001341172.1:p.Ser625Phe
  • NP_001341173.1:p.Ser625Phe
  • NP_001341174.1:p.Ser613Phe
  • NP_001341175.1:p.Ser646Phe
  • NP_001341178.1:p.Ser617Phe
  • NP_001341181.1:p.Ser625Phe
  • NP_001341182.1:p.Ser592Phe
  • NP_001341183.1:p.Ser625Phe
  • NP_001341184.1:p.Ser625Phe
  • NP_001341185.1:p.Ser625Phe
  • NP_001341186.1:p.Ser592Phe
  • NP_001341187.1:p.Ser646Phe
  • NP_001341189.1:p.Ser584Phe
  • NP_001341190.1:p.Ser632Phe
  • NP_001341191.1:p.Ser625Phe
  • NP_001341193.1:p.Ser617Phe
  • NP_001341194.1:p.Ser646Phe
  • NP_001341195.1:p.Ser617Phe
  • NP_001341196.1:p.Ser617Phe
  • NP_001341197.1:p.Ser613Phe
  • NP_001341198.1:p.Ser576Phe
  • NP_001341199.1:p.Ser592Phe
  • NP_001341200.1:p.Ser584Phe
  • NP_001341201.1:p.Ser625Phe
  • NP_001341202.1:p.Ser580Phe
  • NP_001341203.1:p.Ser617Phe
  • NP_001341204.1:p.Ser625Phe
  • NP_001341205.1:p.Ser617Phe
  • NP_001341206.1:p.Ser551Phe
  • NP_001373071.1:p.Ser617Phe
  • NP_001373072.1:p.Ser625Phe
  • NP_001373073.1:p.Ser661Phe
  • NP_001373075.1:p.Ser617Phe
  • NP_001373076.1:p.Ser632Phe
  • NP_001373077.1:p.Ser642Phe
  • NP_001373078.1:p.Ser617Phe
  • NP_001373079.1:p.Ser617Phe
  • NP_001373080.1:p.Ser584Phe
  • NP_001373081.1:p.Ser661Phe
  • NP_001373082.1:p.Ser617Phe
  • NP_001373083.1:p.Ser617Phe
  • NP_001373085.1:p.Ser592Phe
  • NP_001373086.1:p.Ser551Phe
  • NP_001373087.1:p.Ser518Phe
  • NP_001373089.1:p.Ser632Phe
  • NP_001373090.1:p.Ser625Phe
  • NP_001373091.1:p.Ser617Phe
  • NP_001373103.1:p.Ser663Phe
  • NP_001373104.1:p.Ser655Phe
  • NP_001373115.1:p.Ser642Phe
  • NP_001373116.1:p.Ser634Phe
  • NP_066187.2:p.Ser646Phe
  • LRG_327t1:c.1937C>T
  • LRG_327:g.469648C>T
  • NC_000004.11:g.114203886C>T
  • NM_001148.4:c.1937C>T
Protein change:
S518F
Links:
dbSNP: rs786205724
NCBI 1000 Genomes Browser:
rs786205724
Molecular consequence:
  • NM_001127493.3:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001148.6:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354225.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354228.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354230.2:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354231.2:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354232.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354235.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354236.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354237.2:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354239.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354240.2:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354241.2:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354242.2:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354243.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354244.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354245.2:c.1838C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354246.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354249.2:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354252.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354253.2:c.1775C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354254.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354255.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354256.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354257.2:c.1775C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354258.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354260.2:c.1751C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354261.2:c.1895C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354262.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354264.2:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354265.2:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354266.2:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354267.2:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354268.2:c.1838C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354269.3:c.1727C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354270.2:c.1775C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354271.2:c.1751C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354272.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354273.2:c.1739C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354274.2:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354275.2:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354276.2:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354277.2:c.1652C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386142.1:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386143.1:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386144.1:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386146.1:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386147.1:c.1895C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386148.2:c.1925C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386149.1:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386150.1:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386151.1:c.1751C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386152.1:c.1982C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386153.1:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386154.1:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386156.1:c.1775C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386157.1:c.1652C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386158.1:c.1553C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386160.1:c.1895C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386161.1:c.1874C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386162.1:c.1850C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386174.1:c.1988C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386175.1:c.1964C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386186.2:c.1925C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386187.2:c.1901C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_020977.5:c.1937C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
ANK2-related disorder
Synonyms:
ANK2-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004112630PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jun 27, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004112630.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

The ANK2 c.1937C>T variant is predicted to result in the amino acid substitution p.Ser646Phe. This variant has been reported in two families of Gitxsan ancestry with Ankyrin-B syndrome (ABS), long QT syndrome, and structural heart disease, with functional in vitro studies demonstrating this variant disrupted normal localization to the plasma membrane in mouse myocytes (Swayne et al. 2017. PubMed ID: 28196901). Another study showed no significant functional effect of this variant on Cav2.1 levels in HEK293T cells (Choi et al. 2019. PubMed ID: 31477143). The designation of ANK2 as a self-sufficient long QT syndrome susceptibility gene has been questioned due to the high frequency of putative ABS-causative variants in public exomes and the nature of the ABS cardiac phenotype (Giudicessi et al. 2018. PubMed ID: 29661707). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024