chr3-84978677-T-C

Variant names:

• chr3-84978677-T-C
• rs1248858
• NM_001167675.2:c.61+19009T>C

Variant summary

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

The NM_001167675.2(CADM2):​c.61+19009T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.73 in 152,064 control chromosomes in the GnomAD database, including 41,787 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 0.73 (41787 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 3 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.904 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.61+19009T>C		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.61+19009T>C		intron_variant	Intron 1 of 9	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000407528.6	c.61+19009T>C		intron_variant	Intron 1 of 9	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110866 AN: 151946 Hom.: 41737 Cov.: 32

Gnomad AFR AF: 0.911

Gnomad AMI AF: 0.845

Gnomad AMR AF: 0.750

Gnomad ASJ AF: 0.703

Gnomad EAS AF: 0.419

Gnomad SAS AF: 0.622

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.675

Gnomad OTH AF: 0.746

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

GnomAD4 genome AF: 0.730 AC: 110969 AN: 152064 Hom.: 41787 Cov.: 32 AF XY: 0.722 AC XY: 53622 AN XY: 74306

African (AFR) AF: 0.911 AC: 37824 AN: 41504

American (AMR) AF: 0.750 AC: 11437 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.703 AC: 2442 AN: 3472

East Asian (EAS) AF: 0.419 AC: 2160 AN: 5154

South Asian (SAS) AF: 0.620 AC: 2988 AN: 4822

European-Finnish (FIN) AF: 0.538 AC: 5684 AN: 10568

Middle Eastern (MID) AF: 0.656 AC: 193 AN: 294

European-Non Finnish (NFE) AF: 0.675 AC: 45903 AN: 67976

Other (OTH) AF: 0.743 AC: 1567 AN: 2108

Alfa AF: 0.685 Hom.: 26467

Bravo AF: 0.756

Asia WGS AF: 0.557 AC: 1942 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.23
PhyloP100		-1.1
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: rs1248858; hg19: chr3-85027828;