rs13323436

Positions:

• chr3-85453695-T-A
• chr3-85453695-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001167675.2(CADM2):​c.62-272827T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0556 in 152,184 control chromosomes in the GnomAD database, including 359 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 0.056 (359 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.386

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM2	NM_001167675.2	c.62-272827T>A		intron_variant		ENST00000383699.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM2	ENST00000383699.8	c.62-272827T>A		intron_variant		1	NM_001167675.2	A1
CADM2	ENST00000407528.6	c.62-348352T>A		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.0557 AC: 8472 AN: 152066 Hom.: 360 Cov.: 32

Gnomad AFR AF: 0.0153

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0472

Gnomad ASJ AF: 0.0550

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0209

Gnomad FIN AF: 0.103

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0805

Gnomad OTH AF: 0.0609

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

GnomAD4 genome AF: 0.0556 AC: 8464 AN: 152184 Hom.: 359 Cov.: 32 AF XY: 0.0542 AC XY: 4032 AN XY: 74400

Gnomad4 AFR AF: 0.0152

Gnomad4 AMR AF: 0.0471

Gnomad4 ASJ AF: 0.0550

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.103

Gnomad4 NFE AF: 0.0805

Gnomad4 OTH AF: 0.0593

Alfa AF: 0.0359 Hom.: 31

Bravo AF: 0.0508

Asia WGS AF: 0.0110 AC: 39 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.3
DANN	Benign	0.70

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13323436; hg19: chr3-85502845; COSMIC: COSV67378993;