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NM_005633.4(SOS1):c.1645A>G (p.Thr549Ala) AND RASopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 19, 2020
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV001172277.1

Allele description [Variation Report for NM_005633.4(SOS1):c.1645A>G (p.Thr549Ala)]

NM_005633.4(SOS1):c.1645A>G (p.Thr549Ala)

Gene:
SOS1:SOS Ras/Rac guanine nucleotide exchange factor 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p22.1
Genomic location:
Preferred name:
NM_005633.4(SOS1):c.1645A>G (p.Thr549Ala)
HGVS:
  • NC_000002.12:g.39022783T>C
  • NG_007530.1:g.102681A>G
  • NM_001382394.1:c.1624A>G
  • NM_001382395.1:c.1645A>G
  • NM_005633.4:c.1645A>GMANE SELECT
  • NP_001369323.1:p.Thr542Ala
  • NP_001369324.1:p.Thr549Ala
  • NP_005624.2:p.Thr549Ala
  • NP_005624.2:p.Thr549Ala
  • LRG_754t1:c.1645A>G
  • LRG_754:g.102681A>G
  • LRG_754p1:p.Thr549Ala
  • NC_000002.11:g.39249924T>C
  • NM_005633.3(SOS1):c.1645A>G
  • NM_005633.3:c.1645A>G
  • p.Thr549Ala
Protein change:
T542A
Links:
dbSNP: rs1558474335
NCBI 1000 Genomes Browser:
rs1558474335
Molecular consequence:
  • NM_001382394.1:c.1624A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382395.1:c.1645A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005633.4:c.1645A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
RASopathy
Synonyms:
rasopathies; Noonan spectrum disorder
Identifiers:
MONDO: MONDO:0021060; MedGen: C5555857

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001335325ClinGen RASopathy Variant Curation Expert Panel
reviewed by expert panel

(ClinGen RASopathy ACMG Specifications v1)		Uncertain significance
(Mar 19, 2020) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen RASopathy Variant Curation Expert Panel, SCV001335325.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.1645A>G (p.Thr549Ala) variant in SOS1 was absent from large population studies (PM2; gnomad.broadinstitute.org). The variant is located in the SOS1 gene, which has been defined by the ClinGen RASopathy Expert Panel as a gene with a low rate of benign missense variants and pathogenic variants are common (PP2; PMID: 29493581). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. RASopathy-specific ACMG/AMP criteria applied: PM2, PP2.

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

Last Updated: Jun 9, 2022