Variant rs2301611 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_139027.6(ADAMTS13):c.331-42T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 1,578,718 control chromosomes in the GnomAD database, including 1,127 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.028 ( 161 hom., cov: 32)

Exomes 𝑓: 0.012 ( 966 hom. )

Consequence

ADAMTS13
NM_139027.6 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0910

Variant links:

Genes affected

ADAMTS13 (HGNC:1366): (ADAM metallopeptidase with thrombospondin type 1 motif 13) This gene encodes a member of a family of proteins containing several distinct regions, including a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. The enzyme encoded by this gene specifically cleaves von Willebrand Factor (vWF). Defects in this gene are associated with thrombotic thrombocytopenic purpura. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ADAMTS13 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 9-133425487-T-C is Benign according to our data. Variant chr9-133425487-T-C is described in ClinVar as [Benign]. Clinvar id is 1268106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAMTS13	NM_139027.6 linkuse as main transcript	c.331-42T>C		intron_variant		ENST00000355699.7	NP_620596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAMTS13	ENST00000355699.7 linkuse as main transcript	c.331-42T>C		intron_variant		1	NM_139027.6	ENSP00000347927	A2	Q76LX8-2

Frequencies

GnomAD3 genomes

AF:

0.0280

AC:

4251

AN:

152012

Hom.:

160

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0630

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0185

Gnomad ASJ

AF:

0.0182

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0174

Gnomad FIN

AF:

0.0127

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.00422

Gnomad OTH

AF:

0.0216

GnomAD3 exomes

AF:

0.0227

AC:

4748

AN:

209148

Hom.:

214

AF XY:

0.0206

AC XY:

2331

AN XY:

113102

show subpopulations

Gnomad AFR exome

AF:

0.0634

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.0166

Gnomad EAS exome

AF:

0.133

Gnomad SAS exome

AF:

0.0125

Gnomad FIN exome

AF:

0.00893

Gnomad NFE exome

AF:

0.00354

Gnomad OTH exome

AF:

0.0164

GnomAD4 exome

AF:

0.0120

AC:

17060

AN:

1426588

Hom.:

966

Cov.:

AF XY:

0.0119

AC XY:

8413

AN XY:

708218

show subpopulations

Gnomad4 AFR exome

AF:

0.0647

Gnomad4 AMR exome

AF:

0.0260

Gnomad4 ASJ exome

AF:

0.0184

Gnomad4 EAS exome

AF:

0.199

Gnomad4 SAS exome

AF:

0.0126

Gnomad4 FIN exome

AF:

0.00732

Gnomad4 NFE exome

AF:

0.00292

Gnomad4 OTH exome

AF:

0.0180

GnomAD4 genome

AF:

0.0280

AC:

4259

AN:

152130

Hom.:

161

Cov.:

AF XY:

0.0286

AC XY:

2126

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0629

Gnomad4 AMR

AF:

0.0184

Gnomad4 ASJ

AF:

0.0182

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0175

Gnomad4 FIN

AF:

0.0127

Gnomad4 NFE

AF:

0.00422

Gnomad4 OTH

AF:

0.0251

Alfa

AF:

0.0182

Hom.:

Bravo

AF:

0.0310

Asia WGS

AF:

0.0800

AC:

279

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 10, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

5.2

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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