2-206553755-G-C

Variant names:

• chr2-206553755-G-C
• rs10490515
• NM_003812.4:c.933+3595G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003812.4(ADAM23):​c.933+3595G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0271 in 152,196 control chromosomes in the GnomAD database, including 153 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 0.027 (153 hom., cov: 32)
• Consequence: ADAM23 NM_003812.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.299
• Publications: 1 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0976 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.933+3595G>C		intron	N/A	NP_003803.1
	ADAM23	NM_001410985.1		c.933+3595G>C		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.933+3595G>C		intron	N/A	ENSP00000264377.3
	ADAM23	ENST00000374415.7	TSL:5	c.933+3595G>C		intron	N/A	ENSP00000363536.3

Frequencies

GnomAD3 genomes AF: 0.0271 AC: 4128 AN: 152078 Hom.: 153 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0103

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.105

Gnomad SAS AF: 0.0665

Gnomad FIN AF: 0.00953

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00460

Gnomad OTH AF: 0.0206

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

GnomAD4 genome AF: 0.0271 AC: 4129 AN: 152196 Hom.: 153 Cov.: 32 AF XY: 0.0284 AC XY: 2113 AN XY: 74428

African (AFR) AF: 0.0619 AC: 2570 AN: 41518

American (AMR) AF: 0.0103 AC: 158 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0213 AC: 74 AN: 3470

East Asian (EAS) AF: 0.105 AC: 544 AN: 5184

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4826

European-Finnish (FIN) AF: 0.00953 AC: 101 AN: 10594

Middle Eastern (MID) AF: 0.0272 AC: 8 AN: 294

European-Non Finnish (NFE) AF: 0.00459 AC: 312 AN: 67992

Other (OTH) AF: 0.0209 AC: 44 AN: 2108

Alfa AF: 0.00271 Hom.: 0

Bravo AF: 0.0281

Asia WGS AF: 0.0750 AC: 260 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.64
PhyloP100		0.30
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: rs10490515; hg19: chr2-207418479;