chr3-85825014-G-A

Variant names:

• chr3-85825014-G-A
• rs7640855
• NM_001167675.2:c.238+22818G>A

Variant summary

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

The NM_001167675.2(CADM2):​c.238+22818G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,906 control chromosomes in the GnomAD database, including 2,006 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 0.14 (2006 hom., cov: 31)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.578
• Publications: 7 publications found

Genes affected

CADM2 (HGNC:29849): (cell adhesion molecule 2) This gene encodes a member of the synaptic cell adhesion molecule 1 (SynCAM) family which belongs to the immunoglobulin (Ig) superfamily. The encoded protein has three Ig-like domains and a cytosolic protein 4.1 binding site near the C-terminus. Proteins belonging to the protein 4.1 family crosslink spectrin and interact with other cytoskeletal proteins. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

CADM2-AS2 (HGNC:41247): (CADM2 antisense RNA 2)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.238+22818G>A		intron_variant	Intron 3 of 9	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.238+22818G>A		intron_variant	Intron 3 of 9	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000405615.2	c.217+22818G>A		intron_variant	Intron 2 of 9	1		ENSP00000384193.2
CADM2	ENST00000407528.6	c.211+22818G>A		intron_variant	Intron 2 of 9	1		ENSP00000384575.2
CADM2-AS2	ENST00000467225.1	n.50+2987C>T		intron_variant	Intron 1 of 3	5

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21928 AN: 151788 Hom.: 2009 Cov.: 31

Gnomad AFR AF: 0.0592

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.310

Gnomad EAS AF: 0.00465

Gnomad SAS AF: 0.0967

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.172

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

GnomAD4 genome AF: 0.144 AC: 21917 AN: 151906 Hom.: 2006 Cov.: 31 AF XY: 0.140 AC XY: 10361 AN XY: 74238

African (AFR) AF: 0.0590 AC: 2448 AN: 41470

American (AMR) AF: 0.130 AC: 1976 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.310 AC: 1075 AN: 3464

East Asian (EAS) AF: 0.00466 AC: 24 AN: 5150

South Asian (SAS) AF: 0.0970 AC: 468 AN: 4826

European-Finnish (FIN) AF: 0.170 AC: 1791 AN: 10538

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13545 AN: 67930

Other (OTH) AF: 0.171 AC: 359 AN: 2104

Alfa AF: 0.0872 Hom.: 113

Bravo AF: 0.138

Asia WGS AF: 0.0540 AC: 189 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.65
PhyloP100		-0.58
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: rs7640855; hg19: chr3-85874164;