NM_001089.3(ABCA3):c.1502C>A (p.Ala501Glu) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Dec 11, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000155457.2

Allele description [Variation Report for NM_001089.3(ABCA3):c.1502C>A (p.Ala501Glu)]

NM_001089.3(ABCA3):c.1502C>A (p.Ala501Glu)

Gene:
ABCA3:ATP binding cassette subfamily A member 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.3
Genomic location:
Preferred name:
NM_001089.3(ABCA3):c.1502C>A (p.Ala501Glu)
HGVS:
  • NC_000016.10:g.2300114G>T
  • NG_011790.1:g.45633C>A
  • NM_001089.3:c.1502C>AMANE SELECT
  • NP_001080.2:p.Ala501Glu
  • NC_000016.9:g.2350115G>T
  • NM_001089.2:c.1502C>A
Protein change:
A501E
Links:
dbSNP: rs141621969
NCBI 1000 Genomes Browser:
rs141621969
Molecular consequence:
  • NM_001089.3:c.1502C>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
2

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000205148Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Nov 8, 2013)
germlineclinical testing

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

SCV000520868GeneDxcriteria provided, single submitter
Likely benign
(Dec 11, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided22not providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

ABCA3 mutation and pulmonary hypertension: a link with alveolar capillary dysplasia?

Danhaive O, Peca D, Boldrini R.

J Pediatr. 2008 Jun;152(6):891-2. doi: 10.1016/j.jpeds.2008.01.019. No abstract available.

PubMed [citation]
PMID:
18492541

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 Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000205148.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided2not providednot providedclinical testing PubMed (2)

Description

The Ala501Glu variant of ABCA3 has been previously identified in one individual with severe pulmonary hypertension and histological/ultrastructural analyses con sistent with ABCA3 deficiency (Danhaive 2008). This variant is present in 0.46% (40/8600) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs141621969). Alanine (Ala) at positi on 501 is poorly conserved in evolution and other computational analyses (bioche mical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) suggest that the ch ange to glutamic acid (Glu) may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, this variant is less likely disease causing but additional information is needed to fully assess its clinical significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided2not provided2not provided

From GeneDx, SCV000520868.4

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

Description

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.

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

Last Updated: Jul 7, 2021

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