20-37931778-G-C

Position:

• chr20-37931778-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_080607.3(VSTM2L):​c.265G>C​(p.Asp89His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: VSTM2L NM_080607.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.96

Genes affected

VSTM2L (HGNC:16096): (V-set and transmembrane domain containing 2 like) Predicted to enable cell-cell adhesion mediator activity. Involved in negative regulation of neuron apoptotic process. Located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33796912).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3	c.265G>C	p.Asp89His	missense_variant	2/4	ENST00000373461.9	NP_542174.1
VSTM2L	XM_011528530.2	c.265G>C	p.Asp89His	missense_variant	2/3		XP_011526832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2L	ENST00000373461.9	c.265G>C	p.Asp89His	missense_variant	2/4	1	NM_080607.3	ENSP00000362560	P1
VSTM2L	ENST00000448944.1	c.265G>C	p.Asp89His	missense_variant	2/3	3		ENSP00000406537
VSTM2L	ENST00000373459.4	c.122-12203G>C		intron_variant		3		ENSP00000362558

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 27, 2023

The c.265G>C (p.D89H) alteration is located in exon 2 (coding exon 2) of the VSTM2L gene. This alteration results from a G to C substitution at nucleotide position 265, causing the aspartic acid (D) at amino acid position 89 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Pathogenic	29
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0077	T;.
Eigen	Uncertain	0.48
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.85	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	0.83	N;N
REVEL	Benign	0.18
Sift	Benign	0.24	T;T
Sift4G	Benign	0.32	T;T
Polyphen		1.0	D;.
Vest4		0.52
MutPred		0.32		Gain of helix (P = 0.0034);Gain of helix (P = 0.0034);
MVP		0.49
MPC		0.27
ClinPred		0.81	D
GERP RS		4.7
Varity_R		0.14
gMVP		0.39

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: chr20-36560180;