chr3-85456794-A-G

Variant names:

• chr3-85456794-A-G
• rs9309981
• NM_001167675.2:c.62-269728A>G

Variant summary

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

The NM_001167675.2(CADM2):​c.62-269728A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.247 in 151,352 control chromosomes in the GnomAD database, including 4,791 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 0.25 (4791 hom., cov: 31)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.130
• Publications: 5 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=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.62-269728A>G		intron_variant	Intron 1 of 9	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.62-269728A>G		intron_variant	Intron 1 of 9	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000407528.6	c.62-345253A>G		intron_variant	Intron 1 of 9	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes AF: 0.247 AC: 37378 AN: 151244 Hom.: 4791 Cov.: 31

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.373

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.117

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.273

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

GnomAD4 genome AF: 0.247 AC: 37393 AN: 151352 Hom.: 4791 Cov.: 31 AF XY: 0.246 AC XY: 18191 AN XY: 73956

African (AFR) AF: 0.235 AC: 9706 AN: 41274

American (AMR) AF: 0.263 AC: 4001 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1206 AN: 3456

East Asian (EAS) AF: 0.117 AC: 604 AN: 5148

South Asian (SAS) AF: 0.341 AC: 1638 AN: 4806

European-Finnish (FIN) AF: 0.232 AC: 2397 AN: 10336

Middle Eastern (MID) AF: 0.252 AC: 73 AN: 290

European-Non Finnish (NFE) AF: 0.249 AC: 16855 AN: 67814

Other (OTH) AF: 0.272 AC: 573 AN: 2104

Alfa AF: 0.242 Hom.: 773

Bravo AF: 0.248

Asia WGS AF: 0.244 AC: 843 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.1
DANN	Benign	0.57
PhyloP100		0.13
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs9309981; hg19: chr3-85505944;