2-206444049-G-A

Variant names:

• chr2-206444049-G-A
• NM_003812.4:c.183G>A
• ADAM23 p.Arg61Arg

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003812.4(ADAM23):​c.183G>A​(p.Arg61Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000801 in 1,248,086 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: ADAM23 NM_003812.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.820
• Publications: 0 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP7: Synonymous conserved (PhyloP=0.82 with no splicing effect.

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.183G>A	p.Arg61Arg	synonymous	Exon 1 of 26	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.183G>A	p.Arg61Arg	synonymous	Exon 1 of 26	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.183G>A	p.Arg61Arg	synonymous	Exon 1 of 26	ENSP00000264377.3	O75077-1
	ADAM23	ENST00000944282.1		c.183G>A	p.Arg61Arg	synonymous	Exon 1 of 26	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.183G>A	p.Arg61Arg	synonymous	Exon 1 of 27	ENSP00000614335.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.01e-7 AC: 1 AN: 1248086 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 614270

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26090

American (AMR) AF: 0.0000423 AC: 1 AN: 23654

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21028

East Asian (EAS) AF: 0.00 AC: 0 AN: 27852

South Asian (SAS) AF: 0.00 AC: 0 AN: 59578

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4138

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1005916

Other (OTH) AF: 0.00 AC: 0 AN: 50586

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	14
DANN	Benign	0.97
PhyloP100		0.82
PromoterAI		0.0066	Neutral
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

hg19: chr2-207308773;