NM_006939.4(SOS2):c.572C>G (p.Pro191Arg) AND not provided

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Mar 1, 2025
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000513780.25

Allele description [Variation Report for NM_006939.4(SOS2):c.572C>G (p.Pro191Arg)]

NM_006939.4(SOS2):c.572C>G (p.Pro191Arg)

Gene:

SOS2:SOS Ras/Rho guanine nucleotide exchange factor 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q21.3

Genomic location:

Preferred name:

NM_006939.4(SOS2):c.572C>G (p.Pro191Arg)

HGVS:

NC_000014.9:g.50188639G>C
NG_051073.1:g.48055C>G
NM_006939.4:c.572C>GMANE SELECT
NP_008870.2:p.Pro191Arg
NC_000014.8:g.50655357G>C
NM_006939.2:c.572C>G
NM_006939.3:c.572C>G

Protein change:

P191R

Links:

dbSNP: rs72681869

NCBI 1000 Genomes Browser:

rs72681869

Molecular consequence:

NM_006939.4:c.572C>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000609920	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Feb 24, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000698747	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Apr 17, 2017)	germline	clinical testing	LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV001964359	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Likely benign	germline	clinical testing
SCV002545175	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Benign (Mar 1, 2025)	germline	clinical testing	Citation Link,
SCV005212009	Breakthrough Genomics, Breakthrough Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign	germline	not provided	PubMed (1) [See all records that cite this PMID]

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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
not provided	germline	yes	22	not provided	not provided	not provided	not provided	clinical testing, not provided
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	clinical testing

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 Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics, SCV000609920.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	0.005266	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000698747.1

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

Description

Variant summary: The SOS2 c.572C>G (p.Pro191Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 2/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). The variant of interest has been found in a large, broad control population, ExAC in 554/120618 control chromosomes (1 homozygote) at a frequency of 0.004593, which is approximately 1837 times the estimated maximal expected allele frequency of a pathogenic SOS2 variant (0.0000025), suggesting this variant is likely a benign polymorphism. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.

#	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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001964359.1

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

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV002545175.19

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	22	not provided	not provided	clinical testing	not provided

Description

SOS2: BS1, BS2

#	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		22	not provided	not provided	not provided

From Breakthrough Genomics, Breakthrough Genomics, SCV005212009.1

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

#	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: Apr 28, 2025

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