2-206445445-T-C

Position:

• chr2-206445445-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The ENST00000264377.8(ADAM23):​c.353T>C​(p.Ile118Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I118M) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM23 ENST00000264377.8 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.83

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34221816).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.353T>C	p.Ile118Thr	missense_variant	2/26	ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.353T>C	p.Ile118Thr	missense_variant	2/26		NP_001397914.1
ADAM23	XM_005246932.4	c.353T>C	p.Ile118Thr	missense_variant	2/25		XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.353T>C	p.Ile118Thr	missense_variant	2/26	1	NM_003812.4	ENSP00000264377	P4
ADAM23	ENST00000374415.7	c.353T>C	p.Ile118Thr	missense_variant	2/26	5		ENSP00000363536	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

May 20, 2024

The c.353T>C (p.I118T) alteration is located in exon 2 (coding exon 2) of the ADAM23 gene. This alteration results from a T to C substitution at nucleotide position 353, causing the isoleucine (I) at amino acid position 118 to be replaced by a threonine (T). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.19	T;T
Eigen	Benign	-0.093
Eigen_PC	Benign	-0.020
FATHMM_MKL	Uncertain	0.83	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.34	T;T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	1.9	L;.
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-2.6	D;D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D;D
Sift4G	Uncertain	0.0040	D;D
Polyphen		0.28	B;.
Vest4		0.46
MutPred		0.51		Loss of stability (P = 0.0024);Loss of stability (P = 0.0024);
MVP		0.21
MPC		0.12
ClinPred		0.88	D
GERP RS		6.0
Varity_R		0.23
gMVP		0.52

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: chr2-207310169;