rs1256614044

Variant names:

• chr2-206444047-C-A
• rs1256614044
• NM_003812.4:c.181C>A

Your query was ambiguous. Multiple possible variants found:

• chr2-206444047-C-A
• chr2-206444047-C-G
• chr2-206444047-C-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Moderate BP7 BS2

The NM_003812.4(ADAM23):​c.181C>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 0.000004 in 1,250,994 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: 31)
  • Exomes 𝑓: 0.0000040 (0 hom.)
• Consequence: ADAM23 NM_003812.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.660
• 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 -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.2).
• BP7: Synonymous conserved (PhyloP=-0.66 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 5 AD gene.

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.181C>A	p.Arg61Arg	synonymous	Exon 1 of 26	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.181C>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.181C>A	p.Arg61Arg	synonymous	Exon 1 of 26	ENSP00000264377.3	O75077-1
	ADAM23	ENST00000944282.1		c.181C>A	p.Arg61Arg	synonymous	Exon 1 of 26	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.181C>A	p.Arg61Arg	synonymous	Exon 1 of 27	ENSP00000614335.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00 AC: 0 AN: 68364 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000400 AC: 5 AN: 1250994 Hom.: 0 Cov.: 30 AF XY: 0.00000325 AC XY: 2 AN XY: 615730

African (AFR) AF: 0.00 AC: 0 AN: 26124

American (AMR) AF: 0.00 AC: 0 AN: 23814

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21096

East Asian (EAS) AF: 0.00 AC: 0 AN: 27870

South Asian (SAS) AF: 0.00 AC: 0 AN: 60120

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4152

European-Non Finnish (NFE) AF: 0.00000496 AC: 5 AN: 1007614

Other (OTH) AF: 0.00 AC: 0 AN: 50750

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.20
CADD	Benign	13
DANN	Benign	0.92
PhyloP100		-0.66
PromoterAI		0.11	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

Other links and lift over

dbSNP: rs1256614044; hg19: chr2-207308771;