NM_001291303.3(FAT4):c.9313A>G (p.Ser3105Gly) AND Van Maldergem syndrome 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 3, 2018
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:: RCV001004887.2

Allele description [Variation Report for NM_001291303.3(FAT4):c.9313A>G (p.Ser3105Gly)]

NM_001291303.3(FAT4):c.9313A>G (p.Ser3105Gly)

Gene:

FAT4:FAT atypical cadherin 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4q28.1

Genomic location:

Preferred name:

NM_001291303.3(FAT4):c.9313A>G (p.Ser3105Gly)

HGVS:

NC_000004.12:g.125450323A>G
NG_033865.1:g.138912A>G
NM_001291285.3:c.9313A>G
NM_001291303.3:c.9313A>GMANE SELECT
NM_024582.6:c.9307A>G
NP_001278214.1:p.Ser3105Gly
NP_001278232.1:p.Ser3105Gly
NP_078858.4:p.Ser3103Gly
NC_000004.11:g.126371478A>G
NC_000004.11:g.126371478A>G
p.Ser3103Gly

Protein change:

S3103G

Links:

dbSNP: rs764097811

NCBI 1000 Genomes Browser:

rs764097811

Molecular consequence:

NM_001291285.3:c.9313A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001291303.3:c.9313A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_024582.6:c.9307A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Van Maldergem syndrome 2 (VMLDS2)
Identifiers:: MONDO: MONDO:0014242; MedGen: C3809875; Orphanet: 314679; OMIM: 615546

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001164376	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 3, 2018)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001164376

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Dec 3, 2018)

germline

research

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	not provided	not provided	not provided	not provided	not provided	research

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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001164376.1

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

Description

The heterozygous p.Ser3103Gly variant in FAT4 was identified by our study in the compound heterozygous state, with another VUS, in one individual with Van Maldergem syndrome. The p.Ser3103Gly variant in FAT4 has not been previously reported in individuals with Van Maldergem syndrome and has been identified in 0.003249% (1/30778) of South Asian chromosomes, 0.002980% (1/33556) of Latino chromosomes, and 0.002708% (3/110802) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs764097811). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Ser3103Gly variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4 (Richards 2015).

#	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

Last Updated: Mar 30, 2024

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