2-206444047-C-T

Variant names:

• chr2-206444047-C-T
• rs1256614044
• NM_003812.4:c.181C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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. 14/22 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003812.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM23	NM_003812.4	MANE Select	c.181C>T	p.Arg61Trp	missense	Exon 1 of 26	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.181C>T	p.Arg61Trp	missense	Exon 1 of 26	NP_001397914.1	E7EWD3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM23	ENST00000264377.8	TSL:1 MANE Select	c.181C>T	p.Arg61Trp	missense	Exon 1 of 26	ENSP00000264377.3	O75077-1
	ADAM23	ENST00000944282.1		c.181C>T	p.Arg61Trp	missense	Exon 1 of 26	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.181C>T	p.Arg61Trp	missense	Exon 1 of 27	ENSP00000614335.1

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

African (AFR) AF: 0.00 AC: 0 AN: 26124

American (AMR) AF: 0.00 AC: 0 AN: 23814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21096

East Asian (EAS) AF: 0.00 AC: 0 AN: 27872

South Asian (SAS) AF: 0.00 AC: 0 AN: 60120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4152

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1007614

Other (OTH) AF: 0.00 AC: 0 AN: 50750

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.35
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		-0.66
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.090
Sift	Benign	0.11	T
Sift4G	Benign	0.19	T
Polyphen		0.0020	B
Vest4		0.13
MutPred		0.48		Loss of disorder (P = 0.0235)
MVP		0.19
MPC		1.5
ClinPred		0.46	T
GERP RS		3.5
PromoterAI		0.018	Neutral
Varity_R		0.11
gMVP		0.25
Mutation Taster		=83/17	polymorphism

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

Other links and lift over

dbSNP: rs1256614044; hg19: chr2-207308771;