rs9812103

Positions:

• chr3-85937570-A-C

Variant summary

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

The NM_001167675.2(CADM2):​c.791+1713A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 151,770 control chromosomes in the GnomAD database, including 4,039 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 0.22 (4039 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57

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=-0.79).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM2	NM_001167675.2	c.791+1713A>C		intron_variant		ENST00000383699.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM2	ENST00000383699.8	c.791+1713A>C		intron_variant		1	NM_001167675.2	A1
CADM2	ENST00000405615.2	c.770+1713A>C		intron_variant		1
CADM2	ENST00000407528.6	c.764+1713A>C		intron_variant		1		P4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32880 AN: 151652 Hom.: 4036 Cov.: 32

Gnomad AFR AF: 0.338

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.206

Gnomad ASJ AF: 0.210

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.162

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.140

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.213

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

GnomAD4 genome AF: 0.217 AC: 32898 AN: 151770 Hom.: 4039 Cov.: 32 AF XY: 0.215 AC XY: 15981 AN XY: 74170

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.206

Gnomad4 ASJ AF: 0.210

Gnomad4 EAS AF: 0.134

Gnomad4 SAS AF: 0.163

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.211

Alfa AF: 0.170 Hom.: 4661

Bravo AF: 0.224

Asia WGS AF: 0.150 AC: 522 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.4
DANN	Benign	0.87

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: rs9812103; hg19: chr3-85986720;