rs137853147

Variant names:

• chr5-179130005-C-G
• NM_014244.5:c.2384G>C

Your query was ambiguous. Multiple possible variants found:

• chr5-179130005-C-G
• chr5-179130005-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014244.5(ADAMTS2):​c.2384G>C​(p.Trp795Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAMTS2 NM_014244.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.79

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.909

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAMTS2	NM_014244.5	c.2384G>C	p.Trp795Ser	missense_variant	Exon 16 of 22	ENST00000251582.12	NP_055059.2
ADAMTS2	XM_047417895.1	c.1889G>C	p.Trp630Ser	missense_variant	Exon 15 of 21		XP_047273851.1
ADAMTS2	XM_047417896.1	c.1502G>C	p.Trp501Ser	missense_variant	Exon 14 of 20		XP_047273852.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAMTS2	ENST00000251582.12	c.2384G>C	p.Trp795Ser	missense_variant	Exon 16 of 22	1	NM_014244.5	ENSP00000251582.7
ADAMTS2	ENST00000518335.3	c.2384G>C	p.Trp795Ser	missense_variant	Exon 16 of 21	3		ENSP00000489888.2
ADAMTS2	ENST00000698889.1	n.2384G>C		non_coding_transcript_exon_variant	Exon 16 of 21			ENSP00000514008.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.30	D
BayesDel_noAF	Pathogenic	0.19
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.45	T;.
Eigen	Pathogenic	0.78
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	1.0	D
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.91	D;D
MetaSVM	Uncertain	-0.27	T
MutationAssessor	Uncertain	2.8	M;.
PrimateAI	Uncertain	0.71	T
PROVEAN	Pathogenic	-12	D;.
REVEL	Uncertain	0.61
Sift	Uncertain	0.0020	D;.
Sift4G	Pathogenic	0.0	D;.
Polyphen		1.0	D;.
Vest4		0.93
MutPred		0.69		Gain of disorder (P = 0.0014);Gain of disorder (P = 0.0014);
MVP		0.72
MPC		1.6
ClinPred		1.0	D
GERP RS		5.0
Varity_R		0.94
gMVP		0.93

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: chr5-178557006;