3-85771266-A-G

Position:

• chr3-85771266-A-G

Variant summary

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

The NM_001167675.2(CADM2):​c.89-30781A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0533 in 152,196 control chromosomes in the GnomAD database, including 378 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 0.053 (378 hom., cov: 33)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.89-30781A>G		intron_variant		ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.89-30781A>G		intron_variant		1	NM_001167675.2	ENSP00000373200	A1
CADM2	ENST00000405615.2	c.68-30781A>G		intron_variant		1		ENSP00000384193
CADM2	ENST00000407528.6	c.62-30781A>G		intron_variant		1		ENSP00000384575	P4

Frequencies

GnomAD3 genomes AF: 0.0534 AC: 8114 AN: 152078 Hom.: 377 Cov.: 33

Gnomad AFR AF: 0.0851

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0930

Gnomad ASJ AF: 0.0478

Gnomad EAS AF: 0.189

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0132

Gnomad MID AF: 0.0350

Gnomad NFE AF: 0.0177

Gnomad OTH AF: 0.0483

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

GnomAD4 genome AF: 0.0533 AC: 8118 AN: 152196 Hom.: 378 Cov.: 33 AF XY: 0.0569 AC XY: 4236 AN XY: 74416

Gnomad4 AFR AF: 0.0850

Gnomad4 AMR AF: 0.0930

Gnomad4 ASJ AF: 0.0478

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0132

Gnomad4 NFE AF: 0.0177

Gnomad4 OTH AF: 0.0473

Alfa AF: 0.0345 Hom.: 107

Bravo AF: 0.0604

Asia WGS AF: 0.124 AC: 427 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.78

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: rs7621179; hg19: chr3-85820416;