2-206444078-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003812.4(ADAM23):c.212G>A(p.Ser71Asn) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ADAM23 NM_003812.4 missense, splice_region
• Scores: Splicing: ADA: 0.5621
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16491902).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM23	NM_003812.4	c.212G>A	p.Ser71Asn	missense_variant, splice_region_variant	1/26	ENST00000264377.8
ADAM23	NM_001410985.1	c.212G>A	p.Ser71Asn	missense_variant, splice_region_variant	1/26
ADAM23	XM_005246932.4	c.212G>A	p.Ser71Asn	missense_variant, splice_region_variant	1/25

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM23	ENST00000264377.8	c.212G>A	p.Ser71Asn	missense_variant, splice_region_variant	1/26	1	NM_003812.4	P4
ADAM23	ENST00000374415.7	c.212G>A	p.Ser71Asn	missense_variant, splice_region_variant	1/26	5		A1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1207658 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 591406

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 04, 2023

The c.212G>A (p.S71N) alteration is located in exon 1 (coding exon 1) of the ADAM23 gene. This alteration results from a G to A substitution at nucleotide position 212, causing the serine (S) at amino acid position 71 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.63
Cadd	Uncertain	24
Dann	Uncertain	0.99
DEOGEN2	Benign	0.26	T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.023
FATHMM_MKL	Benign	0.45	N
LIST_S2	Benign	0.68	T;T
M_CAP	Benign	0.0061	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.99	N;N;N
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-0.63	N;N
REVEL	Benign	0.054
Sift	Benign	0.041	D;D
Sift4G	Benign	0.56	T;T
Polyphen		0.18	B;.
Vest4		0.18
MutPred		0.33		Loss of glycosylation at S71 (P = 0.0199);Loss of glycosylation at S71 (P = 0.0199);
MVP		0.25
MPC		1.4
ClinPred		0.68	D
GERP RS		4.5
Varity_R		0.13
gMVP		0.20

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.56
dbscSNV1_RF	Benign	0.56
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: chr2-207308802;