2-206490343-C-T

Variant names:

• chr2-206490343-C-T
• rs11891267
• NM_003812.4:c.509+9035C>T

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+9035C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 152,148 control chromosomes in the GnomAD database, including 1,237 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 0.13 (1237 hom., cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.325
• Publications: 3 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.509+9035C>T		intron_variant	Intron 3 of 25	ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.509+9035C>T		intron_variant	Intron 3 of 25		NP_001397914.1
ADAM23	XM_005246932.4	c.509+9035C>T		intron_variant	Intron 3 of 24		XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.509+9035C>T		intron_variant	Intron 3 of 25	1	NM_003812.4	ENSP00000264377.3
ADAM23	ENST00000374415.7	c.509+9035C>T		intron_variant	Intron 3 of 25	5		ENSP00000363536.3

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19105 AN: 152030 Hom.: 1227 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.134

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

GnomAD4 genome AF: 0.126 AC: 19140 AN: 152148 Hom.: 1237 Cov.: 32 AF XY: 0.126 AC XY: 9400 AN XY: 74384

African (AFR) AF: 0.125 AC: 5196 AN: 41492

American (AMR) AF: 0.106 AC: 1622 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3468

East Asian (EAS) AF: 0.143 AC: 742 AN: 5182

South Asian (SAS) AF: 0.109 AC: 525 AN: 4818

European-Finnish (FIN) AF: 0.137 AC: 1447 AN: 10580

Middle Eastern (MID) AF: 0.150 AC: 44 AN: 294

European-Non Finnish (NFE) AF: 0.127 AC: 8605 AN: 68002

Other (OTH) AF: 0.138 AC: 292 AN: 2110

Alfa AF: 0.122 Hom.: 519

Bravo AF: 0.123

Asia WGS AF: 0.125 AC: 435 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.2
DANN	Benign	0.63
PhyloP100		0.33
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: rs11891267; hg19: chr2-207355067;