Variant chr9-133536484-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014694.4(ADAMTSL2):c.-150-79A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.601 in 1,476,806 control chromosomes in the GnomAD database, including 268,778 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.60 ( 27492 hom., cov: 34)

Exomes 𝑓: 0.60 ( 241286 hom. )

Consequence

ADAMTSL2
NM_014694.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -2.16

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 9-133536484-A-C is Benign according to our data. Variant chr9-133536484-A-C is described in ClinVar as [Benign]. Clinvar id is 680461.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.609 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAMTSL2	NM_014694.4 linkuse as main transcript	c.-150-79A>C		intron_variant		ENST00000651351.2

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
ADAMTSL2	ENST00000651351.2 linkuse as main transcript	c.-150-79A>C	intron_variant		NM_014694.4	P1
ADAMTSL2	ENST00000354484.8 linkuse as main transcript	c.-150-79A>C	intron_variant	1		P1
ADAMTSL2	ENST00000393060.1 linkuse as main transcript	c.-150-79A>C	intron_variant	1		P1
ADAMTSL2	ENST00000393061.7 linkuse as main transcript	c.178-79A>C	intron_variant	1

Frequencies

GnomAD3 genomes

AF:

0.595

AC:

90532

AN:

152056

Hom.:

27459

Cov.:

show subpopulations

Gnomad AFR

AF:

0.615

Gnomad AMI

AF:

0.661

Gnomad AMR

AF:

0.456

Gnomad ASJ

AF:

0.546

Gnomad EAS

AF:

0.487

Gnomad SAS

AF:

0.615

Gnomad FIN

AF:

0.687

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.610

Gnomad OTH

AF:

0.565

GnomAD4 exome

AF:

0.601

AC:

796624

AN:

1324632

Hom.:

241286

AF XY:

0.601

AC XY:

386904

AN XY:

644038

show subpopulations

Gnomad4 AFR exome

AF:

0.607

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.544

Gnomad4 EAS exome

AF:

0.554

Gnomad4 SAS exome

AF:

0.608

Gnomad4 FIN exome

AF:

0.688

Gnomad4 NFE exome

AF:

0.608

Gnomad4 OTH exome

AF:

0.586

GnomAD4 genome

AF:

0.595

AC:

90617

AN:

152174

Hom.:

27492

Cov.:

AF XY:

0.596

AC XY:

44326

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.615

Gnomad4 AMR

AF:

0.455

Gnomad4 ASJ

AF:

0.546

Gnomad4 EAS

AF:

0.486

Gnomad4 SAS

AF:

0.615

Gnomad4 FIN

AF:

0.687

Gnomad4 NFE

AF:

0.610

Gnomad4 OTH

AF:

0.567

Alfa

AF:

0.609

Hom.:

3551

Bravo

AF:

0.572

Asia WGS

AF:

0.570

AC:

1984

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Geleophysic dysplasia 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.041

DANN

Benign

0.69

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