chr2-38984217-TAA-T

Variant names:

• chr2-38984217-TAA-T
• rs34248802
• NM_005633.4:c.*1605_*1606delTT

Variant summary

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

The NM_005633.4(SOS1):​c.*1605_*1606delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. The gene SOS1 is included in the ClinGen Criteria Specification Registry.

• Frequency: Genomes: not found (cov: 0)
• Consequence: SOS1 NM_005633.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.220
• Publications: 4 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: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, Genomics England PanelApp
• 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
• 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

Specifications for SOS1 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOS1	NM_005633.4	MANE Select	c.*1605_*1606delTT		3_prime_UTR	Exon 23 of 23	NP_005624.2
	SOS1	NM_001382394.1		c.*1605_*1606delTT		3_prime_UTR	Exon 23 of 23	NP_001369323.1
	SOS1	NM_001382395.1		c.*1605_*1606delTT		3_prime_UTR	Exon 22 of 22	NP_001369324.1	G5E9C8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOS1	ENST00000402219.8	TSL:1 MANE Select	c.*1605_*1606delTT		3_prime_UTR	Exon 23 of 23	ENSP00000384675.2	Q07889-1
	SOS1	ENST00000913800.1		c.*1605_*1606delTT		3_prime_UTR	Exon 21 of 21	ENSP00000583859.1
	SOS1	ENST00000685279.1		c.*1605_*1606delTT		3_prime_UTR	Exon 15 of 15	ENSP00000509424.1	A0A8I5KY52

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22

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: rs34248802; hg19: chr2-39211358;