2-206553755-G-C

Position:

• chr2-206553755-G-C

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.933+3595G>C		intron_variant		ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.933+3595G>C		intron_variant			NP_001397914.1
ADAM23	XM_005246932.4	c.933+3595G>C		intron_variant			XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.933+3595G>C		intron_variant		1	NM_003812.4	ENSP00000264377.3
ADAM23	ENST00000374415.7	c.933+3595G>C		intron_variant		5		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

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.0103

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.105

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.00953

Gnomad4 NFE AF: 0.00459

Gnomad4 OTH AF: 0.0209

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	12
DANN	Benign	0.64

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: rs10490515; hg19: chr2-207418479;