7-87935182-C-G

Position:

• chr7-87935182-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001324418.2(ADAM22):​c.242C>G​(p.Pro81Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.527 in 1,600,082 control chromosomes in the GnomAD database, including 230,061 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.63 (32682 hom., cov: 30)
  • Exomes 𝑓: 0.52 (197379 hom.)
• Consequence: ADAM22 NM_001324418.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• 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]

ADAM22 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=6.7454687E-7).
• BP6: Variant 7-87935182-C-G is Benign according to our data. Variant chr7-87935182-C-G is described in ClinVar as [Benign]. Clinvar id is 1188945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM22	NM_001324418.2	c.242C>G	p.Pro81Arg	missense_variant	2/32	ENST00000413139.2	NP_001311347.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ADAM22	ENST00000413139.2	c.242C>G	p.Pro81Arg	missense_variant	2/32	5	NM_001324418.2	ENSP00000412085.2

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95658 AN: 151782 Hom.: 32609 Cov.: 30

Gnomad AFR AF: 0.912

Gnomad AMI AF: 0.513

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.541

Gnomad SAS AF: 0.369

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.547

Gnomad NFE AF: 0.512

Gnomad OTH AF: 0.634

GnomAD3 exomes AF: 0.537 AC: 118346 AN: 220508 Hom.: 32951 AF XY: 0.523 AC XY: 63389 AN XY: 121302

Gnomad AFR exome AF: 0.922

Gnomad AMR exome AF: 0.561

Gnomad ASJ exome AF: 0.569

Gnomad EAS exome AF: 0.551

Gnomad SAS exome AF: 0.369

Gnomad FIN exome AF: 0.537

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.534

GnomAD4 exome AF: 0.516 AC: 747885 AN: 1448182 Hom.: 197379 Cov.: 54 AF XY: 0.510 AC XY: 367020 AN XY: 719120

Gnomad4 AFR exome AF: 0.927

Gnomad4 AMR exome AF: 0.561

Gnomad4 ASJ exome AF: 0.570

Gnomad4 EAS exome AF: 0.546

Gnomad4 SAS exome AF: 0.366

Gnomad4 FIN exome AF: 0.536

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.534

GnomAD4 genome AF: 0.631 AC: 95797 AN: 151900 Hom.: 32682 Cov.: 30 AF XY: 0.626 AC XY: 46439 AN XY: 74228

Gnomad4 AFR AF: 0.912

Gnomad4 AMR AF: 0.595

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.540

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.512

Gnomad4 OTH AF: 0.633

Alfa AF: 0.493 Hom.: 2674

Bravo AF: 0.649

TwinsUK AF: 0.502 AC: 1862

ALSPAC AF: 0.506 AC: 1952

ESP6500AA AF: 0.892 AC: 3375

ESP6500EA AF: 0.516 AC: 4227

ExAC AF: 0.527 AC: 62567

Asia WGS AF: 0.487 AC: 1699 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Developmental and epileptic encephalopathy, 61 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.052
BayesDel_addAF	Benign	-0.73	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.84
DANN	Benign	0.79
DEOGEN2	Benign	0.0038	.;T;T;.;T;.;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0015	N
LIST_S2	Benign	0.012	T;T;T;T;T;T;T
MetaRNN	Benign	6.7e-7	T;T;T;T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	0.90	L;.;.;L;L;L;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	0.36	N;N;N;N;N;N;N
REVEL	Benign	0.020
Sift	Benign	0.67	T;T;T;T;T;T;T
Sift4G	Benign	0.70	T;T;T;T;T;T;T
Polyphen		0.0010	B;B;.;.;B;B;.
Vest4		0.032
MPC		0.53
ClinPred		0.0023	T
GERP RS		-5.3
Varity_R		0.049
gMVP		0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs2279542; hg19: chr7-87564497; COSMIC: COSV55969663;