9-133536322-C-G

Position:

• chr9-133536322-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014694.4(ADAMTSL2):​c.-150-241C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0193 in 152,338 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.019 (91 hom., cov: 34)
• Consequence: ADAMTSL2 NM_014694.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.423

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-133536322-C-G is Benign according to our data. Variant chr9-133536322-C-G is described in ClinVar as [Benign]. Clinvar id is 1236377.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL2	NM_014694.4	c.-150-241C>G		intron_variant		ENST00000651351.2	NP_055509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTSL2	ENST00000651351.2	c.-150-241C>G		intron_variant			NM_014694.4	ENSP00000498961	P1
ADAMTSL2	ENST00000354484.8	c.-150-241C>G		intron_variant		1		ENSP00000346478	P1
ADAMTSL2	ENST00000393060.1	c.-150-241C>G		intron_variant		1		ENSP00000376780	P1
ADAMTSL2	ENST00000393061.7	c.178-241C>G		intron_variant		1		ENSP00000376781

Frequencies

GnomAD3 genomes AF: 0.0193 AC: 2943 AN: 152220 Hom.: 91 Cov.: 34

Gnomad AFR AF: 0.0660

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00870

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000426

Gnomad OTH AF: 0.0191

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0193 AC: 2943 AN: 152338 Hom.: 91 Cov.: 34 AF XY: 0.0182 AC XY: 1355 AN XY: 74494

Gnomad4 AFR AF: 0.0658

Gnomad4 AMR AF: 0.00869

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000426

Gnomad4 OTH AF: 0.0189

Bravo AF: 0.0229

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 29, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.59
DANN	Benign	0.20

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

Publications

LitVar

Other links and lift over

dbSNP: rs79091755; hg19: chr9-136401444;