NM_001128840.3(CACNA1D):c.1378G>A (p.Gly460Ser) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Oct 24, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000238814.2

Allele description [Variation Report for NM_001128840.3(CACNA1D):c.1378G>A (p.Gly460Ser)]

NM_001128840.3(CACNA1D):c.1378G>A (p.Gly460Ser)

Gene:
CACNA1D:calcium voltage-gated channel subunit alpha1 D [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.1
Genomic location:
Preferred name:
NM_001128840.3(CACNA1D):c.1378G>A (p.Gly460Ser)
HGVS:
  • NC_000003.12:g.53702798G>A
  • NG_032999.1:g.212750G>A
  • NM_000720.4:c.1378G>A
  • NM_001128839.3:c.1378G>A
  • NM_001128840.3:c.1378G>AMANE SELECT
  • NP_000711.1:p.Gly460Ser
  • NP_001122311.1:p.Gly460Ser
  • NP_001122312.1:p.Gly460Ser
  • NC_000003.11:g.53736825G>A
  • NM_000720.2:c.1378G>A
  • NM_000720.3:c.1378G>A
Protein change:
G460S
Links:
dbSNP: rs35874056
NCBI 1000 Genomes Browser:
rs35874056
Molecular consequence:
  • NM_000720.4:c.1378G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128839.3:c.1378G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128840.3:c.1378G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000296958Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphiacriteria provided, single submitter
Uncertain significance
(Aug 10, 2015)
unknownclinical testing

DGD_Variant_Analysis_Guidelines.docx,

Citation Link,

SCV000711549Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely benign
(Oct 24, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided11not providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia, SCV000296958.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000711549.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

p.Gly460Ser in exon 9 of CACNA1D: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. Of note, 23 mammals have a Serine (Ser) at this position despite high nearby amino acid conservation. In addition, computational prediction tools do not suggest a high likelihood of impact to the protein. It has also been identified in 46/126 640 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnom ad.broadinstitute.org; dbSNP rs35874056). ACMG/AMP Criteria applied: BS2 (Richar ds 2015).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided1not provided1not provided

Last Updated: Jul 7, 2021

Support Center