Variant 9-133536945-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_014694.4(ADAMTSL2):c.90+143G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,390,364 control chromosomes in the GnomAD database, including 35,467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.24 ( 4761 hom., cov: 33)

Exomes 𝑓: 0.21 ( 30706 hom. )

Consequence

ADAMTSL2
NM_014694.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.53

Variant links:

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]

ADAMTSL2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 9-133536945-G-T is Benign according to our data. Variant chr9-133536945-G-T is described in ClinVar as [Benign]. Clinvar id is 1225896.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL2	NM_014694.4 linkuse as main transcript	c.90+143G>T		intron_variant		ENST00000651351.2	NP_055509.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris
ADAMTSL2	ENST00000651351.2 linkuse as main transcript	c.90+143G>T	intron_variant		NM_014694.4	ENSP00000498961	P1
ADAMTSL2	ENST00000354484.8 linkuse as main transcript	c.90+143G>T	intron_variant	1		ENSP00000346478	P1
ADAMTSL2	ENST00000393060.1 linkuse as main transcript	c.90+143G>T	intron_variant	1		ENSP00000376780	P1
ADAMTSL2	ENST00000393061.7 linkuse as main transcript	c.417+143G>T	intron_variant	1		ENSP00000376781

Frequencies

GnomAD3 genomes

AF:

0.237

AC:

36052

AN:

152084

Hom.:

4752

Cov.:

show subpopulations

Gnomad AFR

AF:

0.333

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.200

Gnomad ASJ

AF:

0.134

Gnomad EAS

AF:

0.0264

Gnomad SAS

AF:

0.0713

Gnomad FIN

AF:

0.224

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.223

Gnomad OTH

AF:

0.231

GnomAD4 exome

AF:

0.214

AC:

264477

AN:

1238162

Hom.:

30706

AF XY:

0.209

AC XY:

127106

AN XY:

607102

show subpopulations

Gnomad4 AFR exome

AF:

0.329

Gnomad4 AMR exome

AF:

0.148

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.0312

Gnomad4 SAS exome

AF:

0.0766

Gnomad4 FIN exome

AF:

0.228

Gnomad4 NFE exome

AF:

0.230

Gnomad4 OTH exome

AF:

0.207

GnomAD4 genome

AF:

0.237

AC:

36091

AN:

152202

Hom.:

4761

Cov.:

AF XY:

0.232

AC XY:

17260

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.333

Gnomad4 AMR

AF:

0.200

Gnomad4 ASJ

AF:

0.134

Gnomad4 EAS

AF:

0.0264

Gnomad4 SAS

AF:

0.0709

Gnomad4 FIN

AF:

0.224

Gnomad4 NFE

AF:

0.223

Gnomad4 OTH

AF:

0.228

Alfa

AF:

0.227

Hom.:

3607

Bravo

AF:

0.242

Asia WGS

AF:

0.0800

AC:

280

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.35

DANN

Benign

0.62

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over