chr7-87941395-G-A

Variant names:

• chr7-87941395-G-A
• rs470
• NM_001324418.2:c.246+6209G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001324418.2(ADAM22):​c.246+6209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 152,308 control chromosomes in the GnomAD database, including 74,491 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.99 (74491 hom., cov: 32)
• Consequence: ADAM22 NM_001324418.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.564
• Publications: 6 publications found

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 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 61

  Inheritance: Unknown, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001324418.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM22	NM_001324418.2	MANE Select	c.246+6209G>A		intron	N/A	NP_001311347.1	H7C3I4
	ADAM22	NM_001324419.2		c.243+6209G>A		intron	N/A	NP_001311348.1
	ADAM22	NM_001391975.1		c.246+6209G>A		intron	N/A	NP_001378904.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADAM22	ENST00000413139.2	TSL:5 MANE Select	c.246+6209G>A		intron	N/A	ENSP00000412085.2	H7C3I4
	ADAM22	ENST00000265727.11	TSL:1	c.246+6209G>A		intron	N/A	ENSP00000265727.7	Q9P0K1-1
	ADAM22	ENST00000398209.7	TSL:1	c.246+6209G>A		intron	N/A	ENSP00000381267.3	Q9P0K1-2

Frequencies

GnomAD3 genomes AF: 0.989 AC: 150518 AN: 152190 Hom.: 74431 Cov.: 32

Gnomad AFR AF: 0.997

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.993

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.986

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.982

Gnomad OTH AF: 0.993

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.989 AC: 150637 AN: 152308 Hom.: 74491 Cov.: 32 AF XY: 0.989 AC XY: 73671 AN XY: 74456

African (AFR) AF: 0.997 AC: 41421 AN: 41566

American (AMR) AF: 0.993 AC: 15182 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.997 AC: 3462 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5182 AN: 5184

South Asian (SAS) AF: 0.996 AC: 4809 AN: 4828

European-Finnish (FIN) AF: 0.986 AC: 10467 AN: 10614

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.982 AC: 66813 AN: 68036

Other (OTH) AF: 0.993 AC: 2096 AN: 2110

Alfa AF: 0.985 Hom.: 9640

Bravo AF: 0.991

Asia WGS AF: 1.00 AC: 3477 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs470; hg19: chr7-87570710;