rs1555370242

Variant names:

• chr14-50161502-A-G
• rs1555370242
• NM_006939.4:c.1176T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_006939.4(SOS2):​c.1176T>C​(p.Tyr392Tyr) variant causes a synonymous change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SOS2 NM_006939.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.76
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 14-50161502-A-G is Benign according to our data. Variant chr14-50161502-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 475740.Status of the report is criteria_provided_single_submitter, 1 stars.

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.1176T>C	p.Tyr392Tyr	synonymous	Exon 9 of 23	NP_008870.2	Q07890-1
	SOS2	NM_001411020.1		c.1077T>C	p.Tyr359Tyr	synonymous	Exon 8 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.1176T>C	p.Tyr392Tyr	synonymous	Exon 9 of 23	ENSP00000216373.5	Q07890-1
	SOS2	ENST00000543680.5	TSL:1	c.1077T>C	p.Tyr359Tyr	synonymous	Exon 8 of 22	ENSP00000445328.1	Q07890-2
	SOS2	ENST00000555794.2	TSL:1	c.288T>C	p.Tyr96Tyr	synonymous	Exon 3 of 6	ENSP00000484766.1	A0A087X277

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Noonan syndrome 9 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	7.2
DANN	Benign	0.52
PhyloP100		3.8

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: rs1555370242; hg19: chr14-50628220;