2-206509104-A-G

Variant names:

• chr2-206509104-A-G
• rs1025077
• NM_003812.4:c.510-21781A>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.510-21781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.612 in 152,052 control chromosomes in the GnomAD database, including 28,916 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 0.61 (28916 hom., cov: 33)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.160
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.692 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.510-21781A>G		intron	N/A	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.510-21781A>G		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.510-21781A>G		intron	N/A	ENSP00000264377.3	O75077-1
	ADAM23	ENST00000944282.1		c.582-21781A>G		intron	N/A	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.510-21781A>G		intron	N/A	ENSP00000614335.1

Frequencies

GnomAD3 genomes AF: 0.612 AC: 93009 AN: 151934 Hom.: 28895 Cov.: 33

Gnomad AFR AF: 0.581

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.703

Gnomad ASJ AF: 0.623

Gnomad EAS AF: 0.399

Gnomad SAS AF: 0.553

Gnomad FIN AF: 0.591

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.635

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.612 AC: 93066 AN: 152052 Hom.: 28916 Cov.: 33 AF XY: 0.609 AC XY: 45295 AN XY: 74328

African (AFR) AF: 0.581 AC: 24094 AN: 41480

American (AMR) AF: 0.703 AC: 10738 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.623 AC: 2160 AN: 3468

East Asian (EAS) AF: 0.398 AC: 2054 AN: 5164

South Asian (SAS) AF: 0.552 AC: 2655 AN: 4814

European-Finnish (FIN) AF: 0.591 AC: 6237 AN: 10556

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.635 AC: 43161 AN: 67982

Other (OTH) AF: 0.636 AC: 1341 AN: 2110

Alfa AF: 0.628 Hom.: 86664

Bravo AF: 0.622

Asia WGS AF: 0.510 AC: 1772 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.82
PhyloP100		0.16
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1025077;

hg19: chr2-207373828;