2-206486950-C-T

Variant names:

• chr2-206486950-C-T
• rs2113379
• NM_003812.4:c.509+5642C>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+5642C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.703 in 152,056 control chromosomes in the GnomAD database, including 37,908 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 0.70 (37908 hom., cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198
• Publications: 11 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.772 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+5642C>T		intron	N/A	NP_003803.1
	ADAM23	NM_001410985.1		c.509+5642C>T		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+5642C>T		intron	N/A	ENSP00000264377.3
	ADAM23	ENST00000374415.7	TSL:5	c.509+5642C>T		intron	N/A	ENSP00000363536.3

Frequencies

GnomAD3 genomes AF: 0.703 AC: 106833 AN: 151938 Hom.: 37857 Cov.: 32

Gnomad AFR AF: 0.779

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.636

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.641

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.674

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.705

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

GnomAD4 genome AF: 0.703 AC: 106939 AN: 152056 Hom.: 37908 Cov.: 32 AF XY: 0.704 AC XY: 52342 AN XY: 74314

African (AFR) AF: 0.779 AC: 32315 AN: 41494

American (AMR) AF: 0.738 AC: 11264 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.636 AC: 2208 AN: 3470

East Asian (EAS) AF: 0.547 AC: 2832 AN: 5176

South Asian (SAS) AF: 0.640 AC: 3091 AN: 4826

European-Finnish (FIN) AF: 0.710 AC: 7482 AN: 10542

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.672 AC: 45662 AN: 67962

Other (OTH) AF: 0.706 AC: 1491 AN: 2112

Alfa AF: 0.683 Hom.: 58975

Bravo AF: 0.711

Asia WGS AF: 0.641 AC: 2233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.6
DANN	Benign	0.43
PhyloP100		0.20
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: rs2113379; hg19: chr2-207351674;