rs2279542

chr7-87935182-C-Achr7-87935182-C-Gchr7-87935182-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001324418.2(ADAM22):c.242C>A(p.Pro81Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,448,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. 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. P81A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: ADAM22 NM_001324418.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.991

Genes affected

ADAM22 (HGNC:201): (ADAM metallopeptidase domain 22) 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. Unlike other members of the ADAM protein family, the protein encoded by this gene lacks metalloprotease activity since it has no zinc-binding motif. This gene is highly expressed in the brain and may function as an integrin ligand in the brain. In mice, it has been shown to be essential for correct myelination in the peripheral nervous system. Alternative splicing results in several transcript variants.[provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.040428102).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ADAM22	NM_001324418.2	c.242C>A	p.Pro81Gln	missense_variant	2/32	ENST00000413139.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ADAM22	ENST00000413139.2	c.242C>A	p.Pro81Gln	missense_variant	2/32	5	NM_001324418.2	A2

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.90e-7 AC: 1 AN: 1448442 Hom.: 0 Cov.: 54 AF XY: 0.00 AC XY: 0 AN XY: 719272

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: 9.05e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.051
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.68
Cadd	Benign	0.51
Dann	Benign	0.81
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.035	T;T;T;T;T;T;T
M_CAP	Benign	0.0030	T
MetaRNN	Benign	0.040	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.44	N;.;.;N;N;N;.
MutationTaster	Benign	1.0	P;P;P;P;P;P
PrimateAI	Benign	0.24	T
PROVEAN	Benign	0.38	N;N;N;N;N;N;N
REVEL	Benign	0.019
Sift	Benign	0.67	T;T;T;T;T;T;T
Sift4G	Benign	0.53	T;T;T;T;T;T;T
Polyphen		0.0020	B;B;.;.;B;B;.
Vest4		0.068
MutPred		0.42		Gain of disorder (P = 0.1827);Gain of disorder (P = 0.1827);Gain of disorder (P = 0.1827);Gain of disorder (P = 0.1827);Gain of disorder (P = 0.1827);Gain of disorder (P = 0.1827);.;
MVP		0.39
MPC		0.46
ClinPred		0.033	T
GERP RS		-5.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.42

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

LitVar

Other links and lift over

dbSNP: rs2279542; hg19: chr7-87564497;