2-206596435-C-A

Variant names:

• chr2-206596435-C-A
• rs1921663
• NM_003812.4:c.2359+273C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003812.4(ADAM23):​c.2359+273C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,952 control chromosomes in the GnomAD database, including 13,100 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.41 (13100 hom., cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92
• Publications: 4 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

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.2359+273C>A		intron	N/A	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.2359+273C>A		intron	N/A	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.2359+273C>A		intron	N/A	ENSP00000264377.3	O75077-1
	ADAM23	ENST00000944282.1		c.2431+273C>A		intron	N/A	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.2377+273C>A		intron	N/A	ENSP00000614335.1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61837 AN: 151836 Hom.: 13094 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.415

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.407 AC: 61846 AN: 151952 Hom.: 13100 Cov.: 32 AF XY: 0.405 AC XY: 30077 AN XY: 74260

African (AFR) AF: 0.280 AC: 11622 AN: 41438

American (AMR) AF: 0.372 AC: 5676 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1510 AN: 3466

East Asian (EAS) AF: 0.463 AC: 2400 AN: 5180

South Asian (SAS) AF: 0.442 AC: 2132 AN: 4822

European-Finnish (FIN) AF: 0.465 AC: 4894 AN: 10524

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.474 AC: 32190 AN: 67938

Other (OTH) AF: 0.418 AC: 883 AN: 2110

Alfa AF: 0.431 Hom.: 2351

Bravo AF: 0.395

Asia WGS AF: 0.489 AC: 1696 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.041
DANN	Benign	0.33
PhyloP100		-1.9
Mutation Taster		=100/0	polymorphism (auto)

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: rs1921663; hg19: chr2-207461159;