chr9-133537436-G-T

Variant names:

• chr9-133537436-G-T
• rs138540101
• NM_014694.4:c.122G>T

Variant summary

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

The NM_014694.4(ADAMTSL2):​c.122G>T​(p.Gly41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 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: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTSL2 NM_014694.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.36

Genes affected

ADAMTSL2 (HGNC:14631): (ADAMTS like 2) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) and ADAMTS-like protein family. Members of the family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The protein encoded by this gene lacks the protease domain, and is therefore of a member of the the ADAMTS-like protein subfamily. It is a secreted glycoprotein that binds the cell surface and extracellular matrix; it also interacts with latent transforming growth factor beta binding protein 1. Mutations in this gene have been associated with geleophysic dysplasia. [provided by RefSeq, Feb 2009]

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=0.11334905).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTSL2	NM_014694.4	c.122G>T	p.Gly41Val	missense_variant	Exon 3 of 19	ENST00000651351.2	NP_055509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTSL2	ENST00000651351.2	c.122G>T	p.Gly41Val	missense_variant	Exon 3 of 19		NM_014694.4	ENSP00000498961.2
ADAMTSL2	ENST00000393061.7	c.449G>T	p.Gly150Val	missense_variant	Exon 3 of 19	1		ENSP00000376781.3
ADAMTSL2	ENST00000354484.8	c.122G>T	p.Gly41Val	missense_variant	Exon 3 of 19	1		ENSP00000346478.4
ADAMTSL2	ENST00000393060.1	c.122G>T	p.Gly41Val	missense_variant	Exon 3 of 19	1		ENSP00000376780.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1195582 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 576406

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.028	T;T;T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.79	.;T;T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.97	L;.;L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.4	N;N;N
REVEL	Benign	0.043
Sift	Benign	0.24	T;T;T
Sift4G	Benign	0.30	T;T;T
Polyphen		0.0	B;.;B
Vest4		0.14
MutPred		0.34		Loss of disorder (P = 0.0357);.;Loss of disorder (P = 0.0357);
MVP		0.46
MPC		0.54
ClinPred		0.14	T
GERP RS		-1.8
Varity_R		0.067
gMVP		0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs138540101; hg19: chr9-136402558;