2-206596435-C-A

Position:

• chr2-206596435-C-A

Variant summary

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

The NM_003812.4(ADAM23):​c.2359+273C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 151,952 control chromosomes in the GnomAD database, including 13,100 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 0.41 (13100 hom., cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.92

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 (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM23	NM_003812.4	c.2359+273C>A		intron_variant		ENST00000264377.8
ADAM23	NM_001410985.1	c.2359+273C>A		intron_variant
ADAM23	XM_005246932.4	c.2359+273C>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM23	ENST00000264377.8	c.2359+273C>A		intron_variant		1	NM_003812.4	P4
ADAM23	ENST00000374415.7	c.2359+273C>A		intron_variant		5		A1
ADAM23	ENST00000444281.1	c.183+273C>A		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61837 AN: 151836 Hom.: 13094 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.463

Gnomad SAS AF: 0.443

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.474

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.407 AC: 61846 AN: 151952 Hom.: 13100 Cov.: 32 AF XY: 0.405 AC XY: 30077 AN XY: 74260

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.436

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.442

Gnomad4 FIN AF: 0.465

Gnomad4 NFE AF: 0.474

Gnomad4 OTH AF: 0.418

Alfa AF: 0.431 Hom.: 2351

Bravo AF: 0.395

Asia WGS AF: 0.489 AC: 1696 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.041
DANN	Benign	0.33

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: rs1921663; hg19: chr2-207461159;