rs1273376869

Variant names:

• chr14-50188678-T-C
• NM_006939.4:c.533A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-50188678-T-C
• chr14-50188678-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_006939.4(SOS2):​c.533A>G​(p.Gln178Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,446,230 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SOS2 NM_006939.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.98

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.811

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOS2	NM_006939.4	c.533A>G	p.Gln178Arg	missense_variant	Exon 5 of 23	ENST00000216373.10	NP_008870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOS2	ENST00000216373.10	c.533A>G	p.Gln178Arg	missense_variant	Exon 5 of 23	1	NM_006939.4	ENSP00000216373.5
SOS2	ENST00000543680.5	c.533A>G	p.Gln178Arg	missense_variant	Exon 5 of 22	1		ENSP00000445328.1
SOS2	ENST00000556469.5	n.482-6072A>G		intron_variant	Intron 4 of 4	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.91e-7 AC: 1 AN: 1446230 Hom.: 0 Cov.: 29 AF XY: 0.00000139 AC XY: 1 AN XY: 719598

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.04e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.35
BayesDel_addAF	Pathogenic	0.33	D
BayesDel_noAF	Pathogenic	0.23
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.57	D;.
Eigen	Benign	0.093
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D
M_CAP	Benign	0.037	D
MetaRNN	Pathogenic	0.81	D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.78	T
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.63
Sift	Benign	0.11	T;T
Sift4G	Benign	0.076	T;T
Polyphen		0.030	B;.
Vest4		0.86
MutPred		0.54		Loss of solvent accessibility (P = 0.1279);Loss of solvent accessibility (P = 0.1279);
MVP		0.98
MPC		1.3
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.25
gMVP		0.44

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr14-50655396;