19-29527291-G-T

Variant names:

• chr19-29527291-G-T
• rs1435861914
• NM_001146339.2:c.163G>T

Variant summary

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

The NM_001146339.2(VSTM2B):​c.163G>T​(p.Gly55*) variant causes a stop gained change. The variant allele was found at a frequency of 0.000000715 in 1,398,156 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. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: VSTM2B NM_001146339.2 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.90
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSTM2B	NM_001146339.2	c.163G>T	p.Gly55*	stop_gained	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.163G>T	p.Gly55*	stop_gained	Exon 2 of 5	5	NM_001146339.2	ENSP00000335038.6
VSTM2B-DT	ENST00000804084.1	n.116+1750C>A		intron_variant	Intron 1 of 4
VSTM2B-DT	ENST00000804085.1	n.116+1750C>A		intron_variant	Intron 1 of 3
VSTM2B-DT	ENST00000804102.1	n.103+1421C>A		intron_variant	Intron 1 of 3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1398156 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 689596

African (AFR) AF: 0.00 AC: 0 AN: 31578

American (AMR) AF: 0.00 AC: 0 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25164

East Asian (EAS) AF: 0.00 AC: 0 AN: 35702

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79148

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078808

Other (OTH) AF: 0.00 AC: 0 AN: 57976

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.57	D
BayesDel_noAF	Pathogenic	0.58
CADD	Pathogenic	44
DANN	Uncertain	0.99
Eigen	Pathogenic	1.0
Eigen_PC	Pathogenic	0.85
FATHMM_MKL	Uncertain	0.93	D
PhyloP100		4.9
Vest4		0.33
GERP RS		4.6
Mutation Taster		=18/182	disease causing (fs/PTC)

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: rs1435861914; hg19: chr19-30018198;