rs11507716

Variant names:

• chr9-133532073-C-T
• rs11507716
• ENST00000354484.8:c.-648C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001145320.2(ADAMTSL2):​c.-648C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,418 control chromosomes in the GnomAD database, including 1,343 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.12 (1340 hom., cov: 33)
  • Exomes 𝑓: 0.20 (3 hom.)
• Consequence: ADAMTSL2 NM_001145320.2 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.590
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• geleophysic dysplasia 1

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• Ehlers-Danlos syndrome

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145320.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL2	NM_001145320.2		c.-648C>T		upstream_gene	N/A	NP_001138792.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAMTSL2	ENST00000354484.8	TSL:1	c.-648C>T		upstream_gene	N/A	ENSP00000346478.4

Frequencies

GnomAD3 genomes AF: 0.122 AC: 18543 AN: 152174 Hom.: 1338 Cov.: 33

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0909

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.182

Gnomad FIN AF: 0.133

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.153

Gnomad OTH AF: 0.126

GnomAD4 exome AF: 0.202 AC: 25 AN: 124 Hom.: 3 AF XY: 0.192 AC XY: 15 AN XY: 78

African (AFR) AF: 0.00 AC: 0 AN: 4

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0714 AC: 2 AN: 28

Middle Eastern (MID) AF: 0.250 AC: 1 AN: 4

European-Non Finnish (NFE) AF: 0.309 AC: 21 AN: 68

Other (OTH) AF: 0.0625 AC: 1 AN: 16

GnomAD4 genome AF: 0.122 AC: 18555 AN: 152294 Hom.: 1340 Cov.: 33 AF XY: 0.122 AC XY: 9099 AN XY: 74478

African (AFR) AF: 0.0578 AC: 2401 AN: 41566

American (AMR) AF: 0.0909 AC: 1390 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.194 AC: 672 AN: 3470

East Asian (EAS) AF: 0.166 AC: 859 AN: 5174

South Asian (SAS) AF: 0.182 AC: 877 AN: 4830

European-Finnish (FIN) AF: 0.133 AC: 1416 AN: 10614

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.153 AC: 10404 AN: 68022

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.133 Hom.: 972

Bravo AF: 0.112

Asia WGS AF: 0.156 AC: 542 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.0
DANN	Benign	0.62
PhyloP100		-0.59
PromoterAI		0.019	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11507716; hg19: chr9-136397195;