rs775278833

Variant names:

• chr2-206543257-A-G
• 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. Variant got 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

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 Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADAM23	NM_003812.4	c.661A>G	p.Met221Val	missense_variant	Exon 6 of 26	ENST00000264377.8	NP_003803.1
ADAM23	NM_001410985.1	c.661A>G	p.Met221Val	missense_variant	Exon 6 of 26		NP_001397914.1
ADAM23	XM_005246932.4	c.661A>G	p.Met221Val	missense_variant	Exon 6 of 25		XP_005246989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADAM23	ENST00000264377.8	c.661A>G	p.Met221Val	missense_variant	Exon 6 of 26	1	NM_003812.4	ENSP00000264377.3
ADAM23	ENST00000374415.7	c.661A>G	p.Met221Val	missense_variant	Exon 6 of 26	5		ENSP00000363536.3

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;T
Eigen	Uncertain	0.21
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.85	T;T
M_CAP	Benign	0.015	T
MetaRNN	Uncertain	0.69	D;D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-2.5	N;N
REVEL	Uncertain	0.30
Sift	Benign	0.66	T;T
Sift4G	Benign	0.30	T;T
Polyphen		0.60	P;.
Vest4		0.80
MutPred		0.64		Loss of phosphorylation at T226 (P = 0.0884);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-207407981;