rs10194632

Variant names:

• chr2-206493953-G-A
• rs10194632
• NM_003812.4:c.509+12645G>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.509+12645G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,066 control chromosomes in the GnomAD database, including 2,336 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 0.15 (2336 hom., cov: 33)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0930
• Publications: 5 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.279 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM23	NM_003812.4	MANE Select	c.509+12645G>A		intron	N/A	NP_003803.1
	ADAM23	NM_001410985.1		c.509+12645G>A		intron	N/A	NP_001397914.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM23	ENST00000264377.8	TSL:1 MANE Select	c.509+12645G>A		intron	N/A	ENSP00000264377.3
	ADAM23	ENST00000944282.1		c.581+12645G>A		intron	N/A	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.509+12645G>A		intron	N/A	ENSP00000614335.1

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22166 AN: 151948 Hom.: 2335 Cov.: 33

Gnomad AFR AF: 0.283

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.160

Gnomad ASJ AF: 0.0667

Gnomad EAS AF: 0.0863

Gnomad SAS AF: 0.0333

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0772

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.146 AC: 22203 AN: 152066 Hom.: 2336 Cov.: 33 AF XY: 0.148 AC XY: 11000 AN XY: 74328

African (AFR) AF: 0.283 AC: 11744 AN: 41466

American (AMR) AF: 0.160 AC: 2444 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0667 AC: 231 AN: 3464

East Asian (EAS) AF: 0.0859 AC: 444 AN: 5170

South Asian (SAS) AF: 0.0340 AC: 164 AN: 4828

European-Finnish (FIN) AF: 0.159 AC: 1675 AN: 10550

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0772 AC: 5251 AN: 67992

Other (OTH) AF: 0.114 AC: 240 AN: 2112

Alfa AF: 0.142 Hom.: 393

Bravo AF: 0.155

Asia WGS AF: 0.0670 AC: 236 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.6
DANN	Benign	0.21
PhyloP100		0.093
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: rs10194632; hg19: chr2-207358677;