NM_000350.3(ABCA4):c.4948G>A (p.Glu1650Lys) AND not provided

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 5, 2022
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:: RCV001091941.25

Allele description [Variation Report for NM_000350.3(ABCA4):c.4948G>A (p.Glu1650Lys)]

NM_000350.3(ABCA4):c.4948G>A (p.Glu1650Lys)

Genes:

ABCA4:ATP binding cassette subfamily A member 4 [Gene - OMIM - HGNC]
LOC126805793:CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:94486302-94487501 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

1p22.1

Genomic location:

Preferred name:

NM_000350.3(ABCA4):c.4948G>A (p.Glu1650Lys)

HGVS:

NC_000001.11:g.94021310C>T
NG_009073.1:g.104840G>A
NG_009073.2:g.104838G>A
NG_082117.1:g.665C>T
NM_000350.3:c.4948G>AMANE SELECT
NM_001425324.1:c.4726G>A
NP_000341.2:p.Glu1650Lys
NP_001412253.1:p.Glu1576Lys
NC_000001.10:g.94486866C>T
NC_000001.10:g.94486866C>T

Protein change:

E1576K

Links:

dbSNP: rs762754528

NCBI 1000 Genomes Browser:

rs762754528

Molecular consequence:

NM_000350.3:c.4948G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.4726G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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pteridine reductase [Xylella fastidiosa subsp. multiplex]
pteridine reductase [Xylella fastidiosa subsp. multiplex]
gi|2809231711|gnl|PRJNA1026562|R3J2 95|gb|XHF65853.1|

Protein
Ribitol 2-dehydrogenase [Klebsiella pneumoniae]
Ribitol 2-dehydrogenase [Klebsiella pneumoniae]
gi|1738163415|emb|VVK33939.1||gnl|W LY|VVK33939

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001248235	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Jan 1, 2020)	germline	clinical testing	Citation Link,
SCV002113315	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 5, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001248235

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Uncertain significance
(Jan 1, 2020)

germline

clinical testing

Citation Link,

SCV002113315

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 5, 2022)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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 CeGaT Center for Human Genetics Tuebingen, SCV001248235.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002113315.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1650 of the ABCA4 protein (p.Glu1650Lys). This variant is present in population databases (rs762754528, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ABCA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 871794). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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Relating variation to medicine