rs759156036

Variant names:

• chr11-124748409-A-C
• rs759156036
• NM_014312.5:c.832T>G

Your query was ambiguous. Multiple possible variants found:

• chr11-124748409-A-C
• chr11-124748409-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_014312.5(VSIG2):​c.832T>G​(p.Tyr278Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y278H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000055 (0 hom.)
• Consequence: VSIG2 NM_014312.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

Genes affected

VSIG2 (HGNC:17149): (V-set and immunoglobulin domain containing 2) Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35942656).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG2	NM_014312.5	c.832T>G	p.Tyr278Asp	missense_variant	Exon 6 of 7	ENST00000326621.10	NP_055127.2
VSIG2	NM_001329920.2	c.832T>G	p.Tyr278Asp	missense_variant	Exon 6 of 6		NP_001316849.1
VSIG2	XM_047426685.1	c.466T>G	p.Tyr156Asp	missense_variant	Exon 4 of 5		XP_047282641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG2	ENST00000326621.10	c.832T>G	p.Tyr278Asp	missense_variant	Exon 6 of 7	1	NM_014312.5	ENSP00000318684.5
VSIG2	ENST00000403470.1	c.832T>G	p.Tyr278Asp	missense_variant	Exon 6 of 6	2		ENSP00000385013.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000547 AC: 8 AN: 1461266 Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3 AN XY: 726954

African (AFR) AF: 0.00 AC: 0 AN: 33460

American (AMR) AF: 0.00 AC: 0 AN: 44660

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26084

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5750

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111668

Other (OTH) AF: 0.00 AC: 0 AN: 60356

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.016	T;.
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.36	T;T
MetaSVM	Uncertain	-0.21	T
MutationAssessor	Uncertain	2.3	M;M
PhyloP100		2.8
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	-1.6	N;N
REVEL	Uncertain	0.41
Sift	Uncertain	0.013	D;D
Sift4G	Uncertain	0.021	D;D
Polyphen		0.99	D;.
Vest4		0.55
MutPred		0.40		Loss of phosphorylation at Y278 (P = 0.0096);Loss of phosphorylation at Y278 (P = 0.0096);
MVP		0.69
MPC		0.27
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.16
gMVP		0.59
Mutation Taster		=79/21	polymorphism

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: rs759156036; hg19: chr11-124618305;