rs761442415

Variant names:

• chr14-50145212-T-A
• rs761442415
• NM_006939.4:c.2625A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-50145212-T-A
• chr14-50145212-T-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_006939.4(SOS2):​c.2625A>T​(p.Ala875Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000247 in 1,458,836 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000025 (0 hom.)
• Consequence: SOS2 NM_006939.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.136
• Publications: 0 publications found

Genes affected

SOS2 (HGNC:11188): (SOS Ras/Rho guanine nucleotide exchange factor 2) This gene encodes a regulatory protein that is involved in the positive regulation of ras proteins. Mutations in this gene are associated with Noonan Syndrome-9. [provided by RefSeq, Jul 2016]

SOS2 Gene-Disease associations (from GenCC):

• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• Noonan syndrome 9

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P, Ambry Genetics, Genomics England PanelApp
• cardiofaciocutaneous syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Costello syndrome

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome with multiple lentigines

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• Noonan syndrome-like disorder with loose anagen hair

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 14-50145212-T-A is Benign according to our data. Variant chr14-50145212-T-A is described in ClinVar as Benign. ClinVar VariationId is 475748.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.136 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 36 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006939.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOS2	NM_006939.4	MANE Select	c.2625A>T	p.Ala875Ala	synonymous	Exon 16 of 23	NP_008870.2	Q07890-1
	SOS2	NM_001411020.1		c.2526A>T	p.Ala842Ala	synonymous	Exon 15 of 22	NP_001397949.1	Q07890-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOS2	ENST00000216373.10	TSL:1 MANE Select	c.2625A>T	p.Ala875Ala	synonymous	Exon 16 of 23	ENSP00000216373.5	Q07890-1
	SOS2	ENST00000543680.5	TSL:1	c.2526A>T	p.Ala842Ala	synonymous	Exon 15 of 22	ENSP00000445328.1	Q07890-2
	SOS2	ENST00000934708.1		c.2766A>T	p.Ala922Ala	synonymous	Exon 17 of 24	ENSP00000604767.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.000128 AC: 32 AN: 250214 AF XY: 0.0000887

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000934

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000247 AC: 36 AN: 1458836 Hom.: 0 Cov.: 29 AF XY: 0.0000207 AC XY: 15 AN XY: 725868

African (AFR) AF: 0.00 AC: 0 AN: 33378

American (AMR) AF: 0.000787 AC: 35 AN: 44476

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39590

South Asian (SAS) AF: 0.00 AC: 0 AN: 85832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110052

Other (OTH) AF: 0.0000166 AC: 1 AN: 60268

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000491

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Noonan syndrome 9 (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	5.0
DANN	Benign	0.69
PhyloP100		-0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs761442415; hg19: chr14-50611930; COSMIC: COSV99365605;