rs746088783

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_014244.5(ADAMTS2):​c.1278C>T​(p.Gly426=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,575,620 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

ADAMTS2
NM_014244.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter U:1B:1

Conservation

PhyloP100: -1.41
Variant links:
Genes affected
ADAMTS2 (HGNC:218): (ADAM metallopeptidase with thrombospondin type 1 motif 2) This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) 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 encoded preproprotein is proteolytically processed to generate the mature procollagen N-proteinase. This proteinase excises the N-propeptide of the fibrillar procollagens types I-III and type V. Mutations in this gene cause Ehlers-Danlos syndrome type VIIC, a recessively inherited connective-tissue disorder. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 5-179154153-G-A is Benign according to our data. Variant chr5-179154153-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 469662.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.41 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ADAMTS2NM_014244.5 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant 8/22 ENST00000251582.12 NP_055059.2
ADAMTS2NM_021599.4 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant 8/11 NP_067610.1
ADAMTS2XM_047417895.1 linkuse as main transcriptc.783C>T p.Gly261= synonymous_variant 7/21 XP_047273851.1
ADAMTS2XM_047417896.1 linkuse as main transcriptc.396C>T p.Gly132= synonymous_variant 6/20 XP_047273852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ADAMTS2ENST00000251582.12 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant 8/221 NM_014244.5 ENSP00000251582 P2O95450-1
ADAMTS2ENST00000274609.5 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant 8/111 ENSP00000274609 O95450-2
ADAMTS2ENST00000518335.3 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant 8/213 ENSP00000489888 A2
ADAMTS2ENST00000698889.1 linkuse as main transcriptc.1278C>T p.Gly426= synonymous_variant, NMD_transcript_variant 8/21 ENSP00000514008

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152176
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000271
AC:
5
AN:
184470
Hom.:
0
AF XY:
0.0000199
AC XY:
2
AN XY:
100408
show subpopulations
Gnomad AFR exome
AF:
0.0000860
Gnomad AMR exome
AF:
0.000105
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000123
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000176
AC:
25
AN:
1423444
Hom.:
0
Cov.:
32
AF XY:
0.0000198
AC XY:
14
AN XY:
705894
show subpopulations
Gnomad4 AFR exome
AF:
0.0000908
Gnomad4 AMR exome
AF:
0.0000746
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000155
Gnomad4 OTH exome
AF:
0.0000337
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152176
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74338
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000227

ClinVar

Significance: Likely benign
Submissions summary: Uncertain:1Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Ehlers-Danlos syndrome, dermatosparaxis type Uncertain:1Benign:1
Uncertain significance, no assertion criteria providedclinical testingNatera, Inc.Oct 28, 2019- -
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 11, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
0.17
DANN
Benign
0.78

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.

Other links and lift over

dbSNP: rs746088783; hg19: chr5-178581154; API