7-87935073-G-A

Position:

• chr7-87935073-G-A

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.133G>A​(p.Val45Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00231 in 1,614,166 control chromosomes in the GnomAD database, including 98 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0029 (7 hom., cov: 31)
  • Exomes 𝑓: 0.0022 (91 hom.)
• Consequence: ADAM22 NM_001324418.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.04

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=0.002437234).
• BP6: Variant 7-87935073-G-A is Benign according to our data. Variant chr7-87935073-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 713100.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ADAM22	NM_001324418.2	c.133G>A	p.Val45Met	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.133G>A	p.Val45Met	missense_variant	2/32	5	NM_001324418.2	ENSP00000412085.2

Frequencies

GnomAD3 genomes AF: 0.00292 AC: 445 AN: 152188 Hom.: 7 Cov.: 31

Gnomad AFR AF: 0.000869

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00635

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.0530

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000206

Gnomad OTH AF: 0.00479

GnomAD3 exomes AF: 0.00532 AC: 1325 AN: 249042 Hom.: 34 AF XY: 0.00462 AC XY: 625 AN XY: 135232

Gnomad AFR exome AF: 0.000453

Gnomad AMR exome AF: 0.0105

Gnomad ASJ exome AF: 0.000497

Gnomad EAS exome AF: 0.0502

Gnomad SAS exome AF: 0.000654

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.0000798

Gnomad OTH exome AF: 0.00248

GnomAD4 exome AF: 0.00224 AC: 3274 AN: 1461860 Hom.: 91 Cov.: 31 AF XY: 0.00214 AC XY: 1553 AN XY: 727236

Gnomad4 AFR exome AF: 0.000239

Gnomad4 AMR exome AF: 0.0104

Gnomad4 ASJ exome AF: 0.000383

Gnomad4 EAS exome AF: 0.0618

Gnomad4 SAS exome AF: 0.000754

Gnomad4 FIN exome AF: 0.000449

Gnomad4 NFE exome AF: 0.0000674

Gnomad4 OTH exome AF: 0.00281

GnomAD4 genome AF: 0.00293 AC: 447 AN: 152306 Hom.: 7 Cov.: 31 AF XY: 0.00314 AC XY: 234 AN XY: 74480

Gnomad4 AFR AF: 0.000866

Gnomad4 AMR AF: 0.00634

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.0531

Gnomad4 SAS AF: 0.00248

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000206

Gnomad4 OTH AF: 0.00569

Alfa AF: 0.00215 Hom.: 10

Bravo AF: 0.00329

ESP6500AA AF: 0.000251 AC: 1

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00487 AC: 589

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.0000593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Developmental and epileptic encephalopathy, 61 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Sep 07, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	.;T;T;.;T;.;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.29	N
LIST_S2	Uncertain	0.88	D;D;D;D;D;D;D
MetaRNN	Benign	0.0024	T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;.;.;L;L;L;.
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.070	N;N;N;N;N;N;N
REVEL	Benign	0.059
Sift	Benign	0.16	T;T;T;T;T;T;T
Sift4G	Benign	0.16	T;T;T;T;T;T;T
Polyphen		0.075	B;B;.;.;B;B;.
Vest4		0.14
MVP		0.20
MPC		0.51
ClinPred		0.023	T
GERP RS		4.8
Varity_R		0.076
gMVP		0.54

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: rs118019617; hg19: chr7-87564388;