chr2-206445450-T-A

Position:

• chr2-206445450-T-A

Variant summary

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

The NM_003812.4(ADAM23):​c.358T>A​(p.Tyr120Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADAM23 NM_003812.4 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.358T>A	p.Tyr120Asn	missense_variant	2/26	ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.358T>A	p.Tyr120Asn	missense_variant	2/26		NP_001397914.1
ADAM23	XM_005246932.4	c.358T>A	p.Tyr120Asn	missense_variant	2/25		XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.358T>A	p.Tyr120Asn	missense_variant	2/26	1	NM_003812.4	ENSP00000264377	P4
ADAM23	ENST00000374415.7	c.358T>A	p.Tyr120Asn	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.358T>A (p.Y120N) alteration is located in exon 2 (coding exon 2) of the ADAM23 gene. This alteration results from a T to A substitution at nucleotide position 358, causing the tyrosine (Y) at amino acid position 120 to be replaced by an asparagine (N). 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	0.29
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Uncertain	23
DANN	Benign	0.95
DEOGEN2	Benign	0.23	T;T
Eigen	Benign	0.071
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.74	D;D
MetaSVM	Benign	-0.73	T
MutationAssessor	Benign	1.7	L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.22
Sift	Benign	0.31	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.12	B;.
Vest4		0.93
MutPred		0.47		Gain of disorder (P = 0.0207);Gain of disorder (P = 0.0207);
MVP		0.58
MPC		0.43
ClinPred		0.84	D
GERP RS		6.0
Varity_R		0.13
gMVP		0.64

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: chr2-207310174;