rs12494658

Positions:

• chr3-85825326-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.238+23130T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 151,974 control chromosomes in the GnomAD database, including 4,037 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 0.21 (4037 hom., cov: 31)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.460

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.457 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.238+23130T>C		intron_variant		ENST00000383699.8	NP_001161147.1
CADM2-AS2	NR_046752.1	n.50+2675A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.238+23130T>C		intron_variant		1	NM_001167675.2	ENSP00000373200	A1
CADM2	ENST00000405615.2	c.217+23130T>C		intron_variant		1		ENSP00000384193
CADM2	ENST00000407528.6	c.211+23130T>C		intron_variant		1		ENSP00000384575	P4
CADM2-AS2	ENST00000467225.1	n.50+2675A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32454 AN: 151856 Hom.: 4030 Cov.: 31

Gnomad AFR AF: 0.0982

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.189

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.241

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.242

Gnomad OTH AF: 0.224

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

GnomAD4 genome AF: 0.214 AC: 32462 AN: 151974 Hom.: 4037 Cov.: 31 AF XY: 0.218 AC XY: 16196 AN XY: 74268

Gnomad4 AFR AF: 0.0980

Gnomad4 AMR AF: 0.278

Gnomad4 ASJ AF: 0.189

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.309

Gnomad4 FIN AF: 0.241

Gnomad4 NFE AF: 0.242

Gnomad4 OTH AF: 0.231

Alfa AF: 0.242 Hom.: 4546

Bravo AF: 0.214

Asia WGS AF: 0.388 AC: 1347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.4
DANN	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs12494658; hg19: chr3-85874476;