14-50157042-G-C

Variant names:

• chr14-50157042-G-C
• NM_006939.4:c.2014C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006939.4(SOS2):​c.2014C>G​(p.Leu672Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SOS2 NM_006939.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.89

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23685253).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SOS2	NM_006939.4	c.2014C>G	p.Leu672Val	missense_variant	Exon 12 of 23	ENST00000216373.10	NP_008870.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SOS2	ENST00000216373.10	c.2014C>G	p.Leu672Val	missense_variant	Exon 12 of 23	1	NM_006939.4	ENSP00000216373.5
SOS2	ENST00000543680.5	c.1915C>G	p.Leu639Val	missense_variant	Exon 11 of 22	1		ENSP00000445328.1
SOS2	ENST00000555794.2	c.1126C>G	p.Leu376Val	missense_variant	Exon 6 of 6	1		ENSP00000484766.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459944 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726246

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: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T;.
Eigen	Benign	-0.017
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.24	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.076
Sift	Benign	0.10	T;T
Sift4G	Benign	0.18	T;T
Polyphen		0.0020	B;.
Vest4		0.53
MutPred		0.55		Gain of methylation at K673 (P = 0.0341);.;
MVP		0.30
MPC		0.74
ClinPred		0.80	D
GERP RS		5.0
Varity_R		0.64
gMVP		0.67

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: chr14-50623760;