5-179111013-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_014244.5(ADAMTS2):​c.*2854T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00249 in 152,338 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 0.0025 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ADAMTS2
NM_014244.5 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.327
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 Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
Variant 5-179111013-A-G is Benign according to our data. Variant chr5-179111013-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 353039.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00249 (379/152338) while in subpopulation NFE AF= 0.004 (272/68040). AF 95% confidence interval is 0.00361. There are 0 homozygotes in gnomad4. There are 168 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADAMTS2NM_014244.5 linkc.*2854T>C 3_prime_UTR_variant Exon 22 of 22 ENST00000251582.12 NP_055059.2 O95450-1
ADAMTS2XM_047417895.1 linkc.*2854T>C 3_prime_UTR_variant Exon 21 of 21 XP_047273851.1
ADAMTS2XM_047417896.1 linkc.*2854T>C 3_prime_UTR_variant Exon 20 of 20 XP_047273852.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADAMTS2ENST00000251582 linkc.*2854T>C 3_prime_UTR_variant Exon 22 of 22 1 NM_014244.5 ENSP00000251582.7 O95450-1

Frequencies

GnomAD3 genomes
AF:
0.00250
AC:
380
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000700
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00203
Gnomad ASJ
AF:
0.00951
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.000754
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00401
Gnomad OTH
AF:
0.00239
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
4
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
4
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
GnomAD4 genome
AF:
0.00249
AC:
379
AN:
152338
Hom.:
0
Cov.:
33
AF XY:
0.00226
AC XY:
168
AN XY:
74488
show subpopulations
Gnomad4 AFR
AF:
0.000697
Gnomad4 AMR
AF:
0.00203
Gnomad4 ASJ
AF:
0.00951
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.000754
Gnomad4 NFE
AF:
0.00400
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.00250
Hom.:
0
Bravo
AF:
0.00259
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

Ehlers-Danlos syndrome, dermatosparaxis type Benign:1
Jul 08, 2024
Illumina Laboratory Services, Illumina
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
4.6
DANN
Benign
0.55

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: rs11740156; hg19: chr5-178538014; API