rs10514735

Variant names:

• chr3-85749800-A-G
• rs10514735
• NM_001167675.2:c.88+23252A>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.88+23252A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0382 in 152,096 control chromosomes in the GnomAD database, including 242 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 0.038 (242 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.572
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167675.2. 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
	CADM2	NM_001167675.2	MANE Select	c.88+23252A>G		intron	N/A	NP_001161147.1	Q8N3J6-2
	CADM2	NM_001375960.1		c.88+23252A>G		intron	N/A	NP_001362889.1
	CADM2	NM_153184.4		c.67+23252A>G		intron	N/A	NP_694854.2	Q8N3J6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM2	ENST00000383699.8	TSL:1 MANE Select	c.88+23252A>G		intron	N/A	ENSP00000373200.3	Q8N3J6-2
	CADM2	ENST00000405615.2	TSL:1	c.67+23252A>G		intron	N/A	ENSP00000384193.2	Q8N3J6-3
	CADM2	ENST00000407528.6	TSL:1	c.62-52247A>G		intron	N/A	ENSP00000384575.2	Q8N3J6-1

Frequencies

GnomAD3 genomes AF: 0.0382 AC: 5809 AN: 151974 Hom.: 242 Cov.: 32

Gnomad AFR AF: 0.0285

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.0481

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0272

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0384

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

GnomAD4 genome AF: 0.0382 AC: 5809 AN: 152096 Hom.: 242 Cov.: 32 AF XY: 0.0429 AC XY: 3190 AN XY: 74334

African (AFR) AF: 0.0284 AC: 1181 AN: 41544

American (AMR) AF: 0.0876 AC: 1335 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0481 AC: 167 AN: 3470

East Asian (EAS) AF: 0.188 AC: 970 AN: 5150

South Asian (SAS) AF: 0.109 AC: 525 AN: 4830

European-Finnish (FIN) AF: 0.0272 AC: 289 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0177 AC: 1204 AN: 67930

Other (OTH) AF: 0.0375 AC: 79 AN: 2106

Alfa AF: 0.0252 Hom.: 128

Bravo AF: 0.0418

Asia WGS AF: 0.122 AC: 422 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.1
DANN	Benign	0.69
PhyloP100		0.57
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: rs10514735; hg19: chr3-85798950;