3-85770262-A-C

Variant names:

• chr3-85770262-A-C
• rs2325036
• NM_001167675.2:c.89-31785A>C

Variant summary

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

The NM_001167675.2(CADM2):​c.89-31785A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.412 in 151,862 control chromosomes in the GnomAD database, including 13,545 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 0.41 (13545 hom., cov: 31)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.509
• Publications: 15 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.89-31785A>C		intron_variant	Intron 2 of 9	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.89-31785A>C		intron_variant	Intron 2 of 9	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000405615.2	c.68-31785A>C		intron_variant	Intron 1 of 9	1		ENSP00000384193.2
CADM2	ENST00000407528.6	c.62-31785A>C		intron_variant	Intron 1 of 9	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes AF: 0.412 AC: 62485 AN: 151742 Hom.: 13541 Cov.: 31

Gnomad AFR AF: 0.357

Gnomad AMI AF: 0.366

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.358

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.540

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.399

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.402

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

GnomAD4 genome AF: 0.412 AC: 62517 AN: 151862 Hom.: 13545 Cov.: 31 AF XY: 0.425 AC XY: 31532 AN XY: 74220

African (AFR) AF: 0.357 AC: 14781 AN: 41398

American (AMR) AF: 0.512 AC: 7811 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.358 AC: 1243 AN: 3468

East Asian (EAS) AF: 0.760 AC: 3905 AN: 5136

South Asian (SAS) AF: 0.540 AC: 2601 AN: 4818

European-Finnish (FIN) AF: 0.488 AC: 5143 AN: 10548

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25726 AN: 67922

Other (OTH) AF: 0.406 AC: 854 AN: 2104

Alfa AF: 0.394 Hom.: 1621

Bravo AF: 0.412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.49
DANN	Benign	0.50
PhyloP100		0.51
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: rs2325036; hg19: chr3-85819412;