5-179343878-G-C

Variant names:

• chr5-179343878-G-C
• rs755099137
• NM_014244.5:c.423C>G

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_Strong BP7

The NM_014244.5(ADAMTS2):​c.423C>G​(p.Gly141Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 34)
  • Exomes 𝑓: 0.000047 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAMTS2 NM_014244.5 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.669

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP7: Synonymous conserved (PhyloP=-0.669 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.423C>G	p.Gly141Gly	synonymous_variant	Exon 2 of 22	ENST00000251582.12	NP_055059.2
ADAMTS2	NM_021599.4	c.423C>G	p.Gly141Gly	synonymous_variant	Exon 2 of 11		NP_067610.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.423C>G	p.Gly141Gly	synonymous_variant	Exon 2 of 22	1	NM_014244.5	ENSP00000251582.7
ADAMTS2	ENST00000274609.5	c.423C>G	p.Gly141Gly	synonymous_variant	Exon 2 of 11	1		ENSP00000274609.5
ADAMTS2	ENST00000518335.3	c.423C>G	p.Gly141Gly	synonymous_variant	Exon 2 of 21	3		ENSP00000489888.2
ADAMTS2	ENST00000698889.1	n.423C>G		non_coding_transcript_exon_variant	Exon 2 of 21			ENSP00000514008.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD3 exomes AF: 0.000294 AC: 57 AN: 194052 Hom.: 0 AF XY: 0.000273 AC XY: 29 AN XY: 106392

Gnomad AFR exome AF: 0.000373

Gnomad AMR exome AF: 0.000686

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000283

Gnomad SAS exome AF: 0.000113

Gnomad FIN exome AF: 0.000115

Gnomad NFE exome AF: 0.000299

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000467 AC: 67 AN: 1434750 Hom.: 0 Cov.: 75 AF XY: 0.0000548 AC XY: 39 AN XY: 711594

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000798

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000158

Gnomad4 SAS exome AF: 0.0000361

Gnomad4 FIN exome AF: 0.000161

Gnomad4 NFE exome AF: 0.0000154

Gnomad4 OTH exome AF: 0.0000337

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	2.4
DANN	Benign	0.76

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: rs755099137; hg19: chr5-178770879;