rs775278833

Variant names:

• chr2-206543257-A-G
• rs775278833
• NM_003812.4:c.661A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-206543257-A-G
• chr2-206543257-A-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_003812.4(ADAM23):​c.661A>G​(p.Met221Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,642 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M221L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: ADAM23 NM_003812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.40
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.661A>G	p.Met221Val	missense	Exon 6 of 26	NP_003803.1	O75077-1
	ADAM23	NM_001410985.1		c.661A>G	p.Met221Val	missense	Exon 6 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.661A>G	p.Met221Val	missense	Exon 6 of 26	ENSP00000264377.3	O75077-1
	ADAM23	ENST00000944282.1		c.733A>G	p.Met245Val	missense	Exon 6 of 26	ENSP00000614341.1
	ADAM23	ENST00000944276.1		c.661A>G	p.Met221Val	missense	Exon 6 of 27	ENSP00000614335.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461642 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 727126

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86226

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5716

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111886

Other (OTH) AF: 0.00 AC: 0 AN: 60380

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Uncertain	0.077	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.12	T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L
PhyloP100		6.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.30
Sift	Benign	0.66	T
Sift4G	Benign	0.30	T
Polyphen		0.60	P
Vest4		0.80
MutPred		0.64		Loss of phosphorylation at T226 (P = 0.0884)
MVP		0.55
MPC		0.35
ClinPred		0.91	D
GERP RS		5.4
Varity_R		0.24
gMVP		0.71
Mutation Taster		=80/20	polymorphism

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: rs775278833; hg19: chr2-207407981;