NM_016222.4(DDX41):c.1577C>T (p.Ser526Leu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 9, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002576966.3

Allele description [Variation Report for NM_016222.4(DDX41):c.1577C>T (p.Ser526Leu)]

NM_016222.4(DDX41):c.1577C>T (p.Ser526Leu)

Gene:

DDX41:DEAD-box helicase 41 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_016222.4(DDX41):c.1577C>T (p.Ser526Leu)

HGVS:

NC_000005.10:g.177512366G>A
NG_046846.2:g.9596C>T
NM_001321732.2:c.1199C>T
NM_001321830.2:c.1199C>T
NM_016222.4:c.1577C>TMANE SELECT
NP_001308661.1:p.Ser400Leu
NP_001308759.1:p.Ser400Leu
NP_057306.2:p.Ser526Leu
LRG_1386t1:c.1577C>T
LRG_1386:g.9596C>T
LRG_1386p1:p.Ser526Leu
NC_000005.9:g.176939367G>A

Protein change:

S400L

Molecular consequence:

NM_001321732.2:c.1199C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001321830.2:c.1199C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_016222.4:c.1577C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002936591	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 9, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35671390, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002936591

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 9, 2023)

germline

clinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

The genetic landscape of germline DDX41 variants predisposing to myeloid neoplasms.

Li P, Brown S, Williams M, White T, Xie W, Cui W, Peker D, Lei L, Kunder CA, Wang HY, Murray SS, Vagher J, Kovacsovics T, Patel JL.

Blood. 2022 Aug 18;140(7):716-755. doi: 10.1182/blood.2021015135.

PubMed [citation]

PMID:: 35671390
PMCID:: PMC9389629

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002936591.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1901432). This missense change has been observed in individual(s) with a hematological malignancy (PMID: 35671390). This variant is present in population databases (rs774299454, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 526 of the DDX41 protein (p.Ser526Leu).

#	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: Sep 29, 2024

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