9-133536322-C-T

Position:

• chr9-133536322-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_014694.4(ADAMTSL2):​c.-150-241C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0203 in 152,344 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.020 (43 hom., cov: 34)
• Consequence: ADAMTSL2 NM_014694.4 intron
• Clinical Significance: Likely 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=-0.88).
• BP6: Variant 9-133536322-C-T is Benign according to our data. Variant chr9-133536322-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1178978.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.0203 (3097/152344) while in subpopulation AMR AF= 0.0321 (491/15306). AF 95% confidence interval is 0.0297. There are 43 homozygotes in gnomad4. There are 1539 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0204 AC: 3098 AN: 152226 Hom.: 43 Cov.: 34

Gnomad AFR AF: 0.00555

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0321

Gnomad ASJ AF: 0.00518

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0249

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0289

Gnomad OTH AF: 0.0268

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

GnomAD4 genome AF: 0.0203 AC: 3097 AN: 152344 Hom.: 43 Cov.: 34 AF XY: 0.0207 AC XY: 1539 AN XY: 74496

Gnomad4 AFR AF: 0.00553

Gnomad4 AMR AF: 0.0321

Gnomad4 ASJ AF: 0.00518

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00911

Gnomad4 FIN AF: 0.0249

Gnomad4 NFE AF: 0.0288

Gnomad4 OTH AF: 0.0265

Alfa AF: 0.00401 Hom.: 0

Bravo AF: 0.0209

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.6
DANN	Benign	0.32

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;