NM_005359.6(SMAD4):c.903C>G (p.Tyr301Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 14, 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:: RCV000484282.3

Allele description [Variation Report for NM_005359.6(SMAD4):c.903C>G (p.Tyr301Ter)]

NM_005359.6(SMAD4):c.903C>G (p.Tyr301Ter)

Gene:

SMAD4:SMAD family member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

18q21.2

Genomic location:

Preferred name:

NM_005359.6(SMAD4):c.903C>G (p.Tyr301Ter)

HGVS:

NC_000018.10:g.51058455C>G
NG_013013.2:g.95416C>G
NM_005359.6:c.903C>GMANE SELECT
NP_005350.1:p.Tyr301Ter
NP_005350.1:p.Tyr301Ter
LRG_318t1:c.903C>G
LRG_318:g.95416C>G
LRG_318p1:p.Tyr301Ter
NC_000018.9:g.48584825C>G
NM_005359.5:c.903C>G

Protein change:

Y301*

Links:

dbSNP: rs746084369

NCBI 1000 Genomes Browser:

rs746084369

Molecular consequence:

NM_005359.6:c.903C>G - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000572364	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Pathogenic (Jun 14, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000572364

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Pathogenic
(Jun 14, 2018)

germline

clinical testing

Citation Link

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	clinical testing

Details of each submission

From GeneDx, SCV000572364.4

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

Description

This variant is denoted SMAD4 c.903C>G at the cDNA level and p.Tyr301Ter (Y301X) at the protein level. The substitution creates a nonsense variant, which changes a Tyrosine to a premature stop codon (TAC>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, the adjacent variant SMAD4 c.902_903insA, which also results in a premature stop codon at this residue (p.Tyr301Ter), was observed in an individual with multiple juvenile and hyperplastic polyps (Ngeow 2013). Of note, the latter individual also carried a second truncating SMAD4 variant located downstream of Tyr301Ter. We consider SMAD4 Tyr301Ter to be pathogenic.

#	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: Nov 5, 2022

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