rs16838282

Positions:

• chr2-206463871-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000264377.8(ADAM23):​c.433-17361A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 152,340 control chromosomes in the GnomAD database, including 918 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 0.098 (918 hom., cov: 33)
• Consequence: ADAM23 ENST00000264377.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.433-17361A>G		intron_variant		ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.433-17361A>G		intron_variant			NP_001397914.1
ADAM23	XM_005246932.4	c.433-17361A>G		intron_variant			XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.433-17361A>G		intron_variant		1	NM_003812.4	ENSP00000264377	P4
ADAM23	ENST00000374415.7	c.433-17361A>G		intron_variant		5		ENSP00000363536	A1

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14915 AN: 152222 Hom.: 913 Cov.: 33

Gnomad AFR AF: 0.0259

Gnomad AMI AF: 0.126

Gnomad AMR AF: 0.0982

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.145

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.137

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.115

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

GnomAD4 genome AF: 0.0980 AC: 14927 AN: 152340 Hom.: 918 Cov.: 33 AF XY: 0.0996 AC XY: 7416 AN XY: 74470

Gnomad4 AFR AF: 0.0258

Gnomad4 AMR AF: 0.0981

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.137

Gnomad4 NFE AF: 0.127

Gnomad4 OTH AF: 0.119

Alfa AF: 0.103 Hom.: 230

Bravo AF: 0.0924

Asia WGS AF: 0.126 AC: 437 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.9
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs16838282; hg19: chr2-207328595;