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NM_001273.5(CHD4):c.3407C>T (p.Ala1136Val) AND Sifrim-Hitz-Weiss syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 6, 2021
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:
RCV002471359.2

Allele description [Variation Report for NM_001273.5(CHD4):c.3407C>T (p.Ala1136Val)]

NM_001273.5(CHD4):c.3407C>T (p.Ala1136Val)

Gene:
CHD4:chromodomain helicase DNA binding protein 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p13.31
Genomic location:
Preferred name:
NM_001273.5(CHD4):c.3407C>T (p.Ala1136Val)
HGVS:
  • NC_000012.12:g.6588356G>A
  • NG_052823.1:g.24084C>T
  • NM_001273.5:c.3407C>TMANE SELECT
  • NM_001297553.2:c.3386C>T
  • NM_001363606.2:c.3368C>T
  • NP_001264.2:p.Ala1136Val
  • NP_001284482.1:p.Ala1129Val
  • NP_001350535.1:p.Ala1123Val
  • NC_000012.11:g.6697522G>A
  • NM_001273.4:c.3407C>T
Protein change:
A1123V
Molecular consequence:
  • NM_001273.5:c.3407C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001297553.2:c.3386C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001363606.2:c.3368C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Sifrim-Hitz-Weiss syndrome (SIHIWES)
Synonyms:
SIFRIM-HITZ-WEISS MULTIPLE CONGENITAL ANOMALIES-MENTAL RETARDATION SYNDROME
Identifiers:
MONDO: MONDO:0014946; MedGen: C4310688; OMIM: 617159

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002767335Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(May 6, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

The CHD4-related syndrome: a comprehensive investigation of the clinical spectrum, genotype-phenotype correlations, and molecular basis.

Weiss K, Lazar HP, Kurolap A, Martinez AF, Paperna T, Cohen L, Smeland MF, Whalen S, Heide S, Keren B, Terhal P, Irving M, Takaku M, Roberts JD, Petrovich RM, Schrier Vergano SA, Kenney A, Hove H, DeChene E, Quinonez SC, Colin E, Ziegler A, et al.

Genet Med. 2020 Feb;22(2):389-397. doi: 10.1038/s41436-019-0612-0. Epub 2019 Aug 7. Erratum in: Genet Med. 2020 Mar;22(3):669. doi: 10.1038/s41436-019-0727-3.

PubMed [citation]
PMID:
31388190
PMCID:
PMC8900827

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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767335.2

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

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3A. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Sifrim-Hitz-Weiss syndrome (MIM#617159). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0115 - Variants in this gene are known to have variable expressivity. Intellectual disability, developmental and speech delay are the most common features (PMID: 31388190). (I) 0200 - Variant is predicted to result in a missense amino acid change from alanine to valine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0603 - Missense variant in a region that is highly intolerant to missense variation (high constraint region in DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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

Last Updated: Jul 23, 2024