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NM_017721.5(CC2D1A):c.2176C>T (p.Arg726Ter) AND not provided

Germline classification:
Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:
Sep 10, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000578699.2

Allele description [Variation Report for NM_017721.5(CC2D1A):c.2176C>T (p.Arg726Ter)]

NM_017721.5(CC2D1A):c.2176C>T (p.Arg726Ter)

Gene:
CC2D1A:coiled-coil and C2 domain containing 1A [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.12
Genomic location:
Preferred name:
NM_017721.5(CC2D1A):c.2176C>T (p.Arg726Ter)
HGVS:
  • NC_000019.10:g.13927028C>T
  • NG_013089.1:g.25886C>T
  • NM_017721.5:c.2176C>TMANE SELECT
  • NP_060191.3:p.Arg726Ter
  • NC_000019.9:g.14037841C>T
  • NM_017721.4:c.2176C>T
Protein change:
R726*
Links:
dbSNP: rs754855261
NCBI 1000 Genomes Browser:
rs754855261
Molecular consequence:
  • NM_017721.5:c.2176C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000681254GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))
Likely pathogenic
(Dec 12, 2017)
germlineclinical testing

Citation Link,

SCV004449776Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Sep 10, 2023)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

The CC2D1A, a member of a new gene family with C2 domains, is involved in autosomal recessive non-syndromic mental retardation.

Basel-Vanagaite L, Attia R, Yahav M, Ferland RJ, Anteki L, Walsh CA, Olender T, Straussberg R, Magal N, Taub E, Drasinover V, Alkelai A, Bercovich D, Rechavi G, Simon AJ, Shohat M.

J Med Genet. 2006 Mar;43(3):203-10. Epub 2005 Jul 20.

PubMed [citation]
PMID:
16033914
PMCID:
PMC2563235

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From GeneDx, SCV000681254.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The R726X variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R726X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

From Invitae, SCV004449776.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant is present in population databases (rs754855261, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg726*) in the CC2D1A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CC2D1A are known to be pathogenic (PMID: 16033914). This variant has not been reported in the literature in individuals affected with CC2D1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 489260). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Feb 28, 2024