rs769309251

Variant names:

• chr19-29527384-G-A
• rs769309251
• NM_001146339.2:c.256G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-29527384-G-A
• chr19-29527384-G-C
• chr19-29527384-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001146339.2(VSTM2B):​c.256G>A​(p.Ala86Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000299 in 1,537,464 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A86S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000030 (0 hom.)
• Consequence: VSTM2B NM_001146339.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.41
• Publications: 1 publications found

Genes affected

VSTM2B (HGNC:33595): (V-set and transmembrane domain containing 2B) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSTM2B-DT (HGNC:27615): (VSTM2B divergent transcript)

LOC124904683 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09710929).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM2B	NM_001146339.2	c.256G>A	p.Ala86Thr	missense_variant	Exon 2 of 5	ENST00000335523.8	NP_001139811.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSTM2B	ENST00000335523.8	c.256G>A	p.Ala86Thr	missense_variant	Exon 2 of 5	5	NM_001146339.2	ENSP00000335038.6
VSTM2B-DT	ENST00000804084.1	n.116+1657C>T		intron_variant	Intron 1 of 4
VSTM2B-DT	ENST00000804085.1	n.116+1657C>T		intron_variant	Intron 1 of 3
VSTM2B-DT	ENST00000804102.1	n.103+1328C>T		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152118 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000660 AC: 9 AN: 136386 AF XY: 0.0000407

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000170

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000381

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000303 AC: 42 AN: 1385346 Hom.: 0 Cov.: 33 AF XY: 0.0000293 AC XY: 20 AN XY: 683356

African (AFR) AF: 0.00 AC: 0 AN: 30474

American (AMR) AF: 0.000114 AC: 4 AN: 35092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24860

East Asian (EAS) AF: 0.00 AC: 0 AN: 35036

South Asian (SAS) AF: 0.0000513 AC: 4 AN: 77974

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43396

Middle Eastern (MID) AF: 0.000181 AC: 1 AN: 5526

European-Non Finnish (NFE) AF: 0.0000270 AC: 29 AN: 1075394

Other (OTH) AF: 0.0000695 AC: 4 AN: 57594

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152118 Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2 AN XY: 74318

African (AFR) AF: 0.0000241 AC: 1 AN: 41440

American (AMR) AF: 0.0000655 AC: 1 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67998

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000444 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0025	T
Eigen	Benign	0.090
Eigen_PC	Benign	0.17
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.034	D
MetaRNN	Benign	0.097	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.0	L
PhyloP100		3.4
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.31	N
REVEL	Benign	0.079
Sift	Benign	0.70	T
Sift4G	Benign	0.47	T
Polyphen		0.82	P
Vest4		0.16
MutPred		0.37		Gain of relative solvent accessibility (P = 0.0082);
MVP		0.20
ClinPred		0.10	T
GERP RS		3.4
Varity_R		0.065
gMVP		0.26
Mutation Taster		=76/24	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: rs769309251; hg19: chr19-30018291; COSMIC: COSV59262809; COSMIC: COSV59262809;