2-206537710-A-G

Variant names:

• chr2-206537710-A-G
• rs3755224
• NM_003812.4:c.574-4342A>G

Variant summary

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

The NM_003812.4(ADAM23):​c.574-4342A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 152,190 control chromosomes in the GnomAD database, including 1,044 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 0.10 (1044 hom., cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.639
• 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.574-4342A>G		intron_variant	Intron 4 of 25	ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.574-4342A>G		intron_variant	Intron 4 of 25		NP_001397914.1
ADAM23	XM_005246932.4	c.574-4342A>G		intron_variant	Intron 4 of 24		XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.574-4342A>G		intron_variant	Intron 4 of 25	1	NM_003812.4	ENSP00000264377.3
ADAM23	ENST00000374415.7	c.574-4342A>G		intron_variant	Intron 4 of 25	5		ENSP00000363536.3

Frequencies

GnomAD3 genomes AF: 0.104 AC: 15858 AN: 152072 Hom.: 1038 Cov.: 32

Gnomad AFR AF: 0.0269

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.101

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.104 AC: 15871 AN: 152190 Hom.: 1044 Cov.: 32 AF XY: 0.106 AC XY: 7907 AN XY: 74418

African (AFR) AF: 0.0268 AC: 1115 AN: 41552

American (AMR) AF: 0.101 AC: 1544 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 564 AN: 3470

East Asian (EAS) AF: 0.209 AC: 1079 AN: 5166

South Asian (SAS) AF: 0.123 AC: 594 AN: 4824

European-Finnish (FIN) AF: 0.156 AC: 1650 AN: 10600

Middle Eastern (MID) AF: 0.136 AC: 40 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8914 AN: 67978

Other (OTH) AF: 0.120 AC: 254 AN: 2108

Alfa AF: 0.111 Hom.: 193

Bravo AF: 0.0970

Asia WGS AF: 0.155 AC: 538 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	2.9
DANN	Benign	0.76
PhyloP100		0.64
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: rs3755224; hg19: chr2-207402434;