2-206444047-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003812.4(ADAM23):c.181C>T(p.Arg61Trp) variant causes a missense 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM23 NM_003812.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.660

Genes affected

ADAM23 (HGNC:202): (ADAM metallopeptidase domain 23) This gene encodes a member of the ADAM (a disintegrin and metalloprotease domain) family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. It is reported that inactivation of this gene is associated with tumorigenesis in human cancers. [provided by RefSeq, May 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11697361).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM23	NM_003812.4	c.181C>T	p.Arg61Trp	missense_variant	1/26	ENST00000264377.8
ADAM23	NM_001410985.1	c.181C>T	p.Arg61Trp	missense_variant	1/26
ADAM23	XM_005246932.4	c.181C>T	p.Arg61Trp	missense_variant	1/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM23	ENST00000264377.8	c.181C>T	p.Arg61Trp	missense_variant	1/26	1	NM_003812.4	P4
ADAM23	ENST00000374415.7	c.181C>T	p.Arg61Trp	missense_variant	1/26	5		A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1250996 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 615732

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 20, 2023

The c.181C>T (p.R61W) alteration is located in exon 1 (coding exon 1) of the ADAM23 gene. This alteration results from a C to T substitution at nucleotide position 181, causing the arginine (R) at amino acid position 61 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.80	T;T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.78	N;N;N
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.81	N;N
REVEL	Benign	0.090
Sift	Benign	0.11	T;T
Sift4G	Benign	0.19	T;T
Polyphen		0.0020	B;.
Vest4		0.13
MutPred		0.48		Loss of disorder (P = 0.0235);Loss of disorder (P = 0.0235);
MVP		0.19
MPC		1.5
ClinPred		0.46	T
GERP RS		3.5
Varity_R		0.11
gMVP		0.25

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: chr2-207308771;