rs13379306

Variant names:

• chr14-50156098-C-A
• rs13379306
• ENST00000555794.2:c.*813G>T

Your query was ambiguous. Multiple possible variants found:

• chr14-50156098-C-A
• chr14-50156098-C-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000555794.2(SOS2):​c.*813G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.154 in 151,812 control chromosomes in the GnomAD database, including 2,406 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2406 hom., cov: 31)
  • Failed GnomAD Quality Control
• Consequence: SOS2 ENST00000555794.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 3 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: ClinGen, Orphanet
• Noonan syndrome 9

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOS2	NM_006939.4	c.2057+901G>T		intron_variant	Intron 12 of 22	ENST00000216373.10	NP_008870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOS2	ENST00000555794.2	c.*813G>T		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000484766.1
SOS2	ENST00000216373.10	c.2057+901G>T		intron_variant	Intron 12 of 22	1	NM_006939.4	ENSP00000216373.5
SOS2	ENST00000543680.5	c.1958+901G>T		intron_variant	Intron 11 of 21	1		ENSP00000445328.1

Frequencies

GnomAD3 genomes AF: 0.155 AC: 23437 AN: 151692 Hom.: 2407 Cov.: 31

Gnomad AFR AF: 0.0515

Gnomad AMI AF: 0.188

Gnomad AMR AF: 0.326

Gnomad ASJ AF: 0.178

Gnomad EAS AF: 0.238

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.154

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.179

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.154 AC: 23433 AN: 151812 Hom.: 2406 Cov.: 31 AF XY: 0.158 AC XY: 11716 AN XY: 74170

African (AFR) AF: 0.0514 AC: 2128 AN: 41398

American (AMR) AF: 0.326 AC: 4962 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.178 AC: 616 AN: 3470

East Asian (EAS) AF: 0.238 AC: 1230 AN: 5174

South Asian (SAS) AF: 0.175 AC: 837 AN: 4796

European-Finnish (FIN) AF: 0.154 AC: 1619 AN: 10520

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.168 AC: 11436 AN: 67900

Other (OTH) AF: 0.183 AC: 385 AN: 2106

Alfa AF: 0.144 Hom.: 192

Bravo AF: 0.166

Asia WGS AF: 0.208 AC: 722 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.44
DANN	Benign	0.32
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs13379306; hg19: chr14-50622816;