Variant 9-133534854-G-GC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1BP6_ModerateBS1BS2

The ENST00000393061.7(ADAMTSL2):c.116dup(p.Ser40ValfsTer33) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00162 in 1,495,150 control chromosomes in the GnomAD database, including 39 homozygotes. Variant has been reported in ClinVar as Likely benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.0011 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 37 hom. )

Consequence

ADAMTSL2
ENST00000393061.7 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.259

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 Likely_benign. Variant got -2 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 9-133534854-G-GC is Benign according to our data. Variant chr9-133534854-G-GC is described in ClinVar as [Likely_benign]. Clinvar id is 365569.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0011 (168/152222) while in subpopulation SAS AF= 0.0219 (106/4830). AF 95% confidence interval is 0.0186. There are 2 homozygotes in gnomad4. There are 102 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTSL2	NM_014694.4 linkuse as main transcript	c.-212dup		5_prime_UTR_variant	1/19	ENST00000651351.2	NP_055509.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
ADAMTSL2	ENST00000393061.7 linkuse as main transcript	c.116dup	p.Ser40ValfsTer33	frameshift_variant	1/19	1		ENSP00000376781
ADAMTSL2	ENST00000651351.2 linkuse as main transcript	c.-212dup		5_prime_UTR_variant	1/19		NM_014694.4	ENSP00000498961	P1
ADAMTSL2	ENST00000393060.1 linkuse as main transcript	c.-212dup		5_prime_UTR_variant	1/19	1		ENSP00000376780	P1
ADAMTSL2	ENST00000354484.8 linkuse as main transcript	c.-150-1707dup		intron_variant		1		ENSP00000346478	P1

Frequencies

GnomAD3 genomes

AF:

0.00110

AC:

168

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000772

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000353

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00418

AC:

421

AN:

100766

Hom.:

AF XY:

0.00530

AC XY:

294

AN XY:

55500

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000716

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000612

Gnomad SAS exome

AF:

0.0217

Gnomad FIN exome

AF:

0.000488

Gnomad NFE exome

AF:

0.000612

Gnomad OTH exome

AF:

0.00213

GnomAD4 exome

AF:

0.00168

AC:

2253

AN:

1342928

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1449

AN XY:

659696

show subpopulations

Gnomad4 AFR exome

AF:

0.000178

Gnomad4 AMR exome

AF:

0.00128

Gnomad4 ASJ exome

AF:

0.0000423

Gnomad4 EAS exome

AF:

0.000296

Gnomad4 SAS exome

AF:

0.0215

Gnomad4 FIN exome

AF:

0.000279

Gnomad4 NFE exome

AF:

0.000473

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00110

AC:

168

AN:

152222

Hom.:

Cov.:

AF XY:

0.00137

AC XY:

102

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000774

Gnomad4 SAS

AF:

0.0219

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000510

Hom.:

Bravo

AF:

0.000533

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Geleophysic dysplasia

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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