NM_000382.3(ALDH3A2):c.777G>A (p.Trp259Ter) AND Sjögren-Larsson syndrome

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 22, 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:: RCV000991399.4

Allele description [Variation Report for NM_000382.3(ALDH3A2):c.777G>A (p.Trp259Ter)]

NM_000382.3(ALDH3A2):c.777G>A (p.Trp259Ter)

Gene:

ALDH3A2:aldehyde dehydrogenase 3 family member A2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p11.2

Genomic location:

Preferred name:

NM_000382.3(ALDH3A2):c.777G>A (p.Trp259Ter)

HGVS:

NC_000017.11:g.19657841G>A
NG_007095.2:g.14091G>A
NM_000382.3:c.777G>AMANE SELECT
NM_001031806.2:c.777G>A
NM_001369136.1:c.777G>A
NM_001369137.2:c.777G>A
NM_001369138.2:c.777G>A
NM_001369139.1:c.777G>A
NM_001369146.2:c.777G>A
NM_001369148.2:c.198G>A
NP_000373.1:p.Trp259Ter
NP_001026976.1:p.Trp259Ter
NP_001356065.1:p.Trp259Ter
NP_001356066.1:p.Trp259Ter
NP_001356067.1:p.Trp259Ter
NP_001356068.1:p.Trp259Ter
NP_001356075.1:p.Trp259Ter
NP_001356077.1:p.Trp66Ter
NC_000017.10:g.19561154G>A
NC_000017.10:g.19561154G>A

Protein change:

W259*

Links:

dbSNP: rs1555533754

NCBI 1000 Genomes Browser:

rs1555533754

Molecular consequence:

NM_000382.3:c.777G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001031806.2:c.777G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369136.1:c.777G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369137.2:c.777G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369138.2:c.777G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369139.1:c.777G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369146.2:c.777G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001369148.2:c.198G>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Sjögren-Larsson syndrome (SLS)
Synonyms:: FATTY ALCOHOL:NAD+ OXIDOREDUCTASE DEFICIENCY; Fatty aldehyde dehydrogenase deficiency; FADH deficiency; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010031; MedGen: C0037231; Orphanet: 816; OMIM: 270200

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001142794	Hadassah Hebrew University Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jun 20, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002521856	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 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

SCV001142794

Hadassah Hebrew University Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jun 20, 2019)

germline

clinical testing

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

SCV002521856

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 22, 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	1	not provided	clinical 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 Hadassah Hebrew University Medical Center, SCV001142794.2

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

#	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		not provided	not provided	not provided	not provided

From 3billion, SCV002521856.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense): predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic without evidence for the classification (ClinVar ID: VCV000804419). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 29, 2024

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