2-38997474-GT-G

Variant names:

• chr2-38997474-GT-G
• rs869215095
• NM_005633.4:c.2792-50delA

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_005633.4(SOS1):​c.2792-50delA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: SOS1 NM_005633.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.245
• Publications: 0 publications found

Genes affected

SOS1 (HGNC:11187): (SOS Ras/Rac guanine nucleotide exchange factor 1) This gene encodes a protein that is a guanine nucleotide exchange factor for RAS proteins, membrane proteins that bind guanine nucleotides and participate in signal transduction pathways. GTP binding activates and GTP hydrolysis inactivates RAS proteins. The product of this gene may regulate RAS proteins by facilitating the exchange of GTP for GDP. Mutations in this gene are associated with gingival fibromatosis 1 and Noonan syndrome type 4. [provided by RefSeq, Jul 2008]

SOS1 Gene-Disease associations (from GenCC):

• Noonan syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Noonan syndrome 4

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, G2P, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• fibromatosis, gingival, 1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hereditary gingival fibromatosis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• cardiofaciocutaneous syndrome

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005633.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOS1	NM_005633.4	MANE Select	c.2792-50delA		intron	N/A	NP_005624.2
	SOS1	NM_001382394.1		c.2771-50delA		intron	N/A	NP_001369323.1
	SOS1	NM_001382395.1		c.2792-50delA		intron	N/A	NP_001369324.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOS1	ENST00000402219.8	TSL:1 MANE Select	c.2792-50delA		intron	N/A	ENSP00000384675.2
	SOS1	ENST00000395038.6	TSL:5	c.2792-50delA		intron	N/A	ENSP00000378479.2
	SOS1	ENST00000692089.1		c.2681-50delA		intron	N/A	ENSP00000508626.1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000265 AC: 3 AN: 1131190 Hom.: 0 Cov.: 17 AF XY: 0.00000173 AC XY: 1 AN XY: 578384

African (AFR) AF: 0.00 AC: 0 AN: 27170

American (AMR) AF: 0.00 AC: 0 AN: 43038

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23910

East Asian (EAS) AF: 0.00 AC: 0 AN: 37932

South Asian (SAS) AF: 0.00 AC: 0 AN: 78752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 45012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5050

European-Non Finnish (NFE) AF: 0.00000365 AC: 3 AN: 820846

Other (OTH) AF: 0.00 AC: 0 AN: 49480

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.24

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs869215095; hg19: chr2-39224615;