chr5-179207680-C-A

Variant names:

• chr5-179207680-C-A
• NM_014244.5:c.724G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_014244.5(ADAMTS2):​c.724G>T​(p.Ala242Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,798 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: ADAMTS2 NM_014244.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.058436394).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.724G>T	p.Ala242Ser	missense_variant	Exon 4 of 22	ENST00000251582.12	NP_055059.2
ADAMTS2	NM_021599.4	c.724G>T	p.Ala242Ser	missense_variant	Exon 4 of 11		NP_067610.1
ADAMTS2	XM_047417895.1	c.229G>T	p.Ala77Ser	missense_variant	Exon 3 of 21		XP_047273851.1
ADAMTS2	XM_047417896.1	c.-159G>T		5_prime_UTR_variant	Exon 2 of 20		XP_047273852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.724G>T	p.Ala242Ser	missense_variant	Exon 4 of 22	1	NM_014244.5	ENSP00000251582.7
ADAMTS2	ENST00000274609.5	c.724G>T	p.Ala242Ser	missense_variant	Exon 4 of 11	1		ENSP00000274609.5
ADAMTS2	ENST00000518335.3	c.724G>T	p.Ala242Ser	missense_variant	Exon 4 of 21	3		ENSP00000489888.2
ADAMTS2	ENST00000698889.1	n.724G>T		non_coding_transcript_exon_variant	Exon 4 of 21			ENSP00000514008.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460798 Hom.: 0 Cov.: 37 AF XY: 0.00 AC XY: 0 AN XY: 726776

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

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: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.0
DANN	Benign	0.46
DEOGEN2	Benign	0.13	T;.;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.21	N
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.058	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.3	L;.;L
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.38	N;.;N
REVEL	Benign	0.034
Sift	Benign	0.75	T;.;T
Sift4G	Benign	0.82	T;.;T
Polyphen		0.028	B;.;B
Vest4		0.15
MutPred		0.30		Gain of phosphorylation at A242 (P = 0.0162);Gain of phosphorylation at A242 (P = 0.0162);Gain of phosphorylation at A242 (P = 0.0162);
MVP		0.40
MPC		0.37
ClinPred		0.013	T
GERP RS		0.87
Varity_R		0.034
gMVP		0.43

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr5-178634681;