rs9866277

Variant names:

• chr3-86056190-G-A
• rs9866277
• NM_001167675.2:c.971-9415G>A

Variant summary

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

The NM_001167675.2(CADM2):​c.971-9415G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.196 in 152,078 control chromosomes in the GnomAD database, including 3,090 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 0.20 (3090 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• Publications: 4 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=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.971-9415G>A		intron_variant	Intron 8 of 9	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.971-9415G>A		intron_variant	Intron 8 of 9	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000405615.2	c.1070-9415G>A		intron_variant	Intron 8 of 9	1		ENSP00000384193.2
CADM2	ENST00000407528.6	c.1064-9415G>A		intron_variant	Intron 8 of 9	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29848 AN: 151960 Hom.: 3088 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.209

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.193

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

GnomAD4 genome AF: 0.196 AC: 29875 AN: 152078 Hom.: 3090 Cov.: 32 AF XY: 0.199 AC XY: 14765 AN XY: 74308

African (AFR) AF: 0.246 AC: 10202 AN: 41502

American (AMR) AF: 0.199 AC: 3035 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.209 AC: 725 AN: 3472

East Asian (EAS) AF: 0.266 AC: 1368 AN: 5134

South Asian (SAS) AF: 0.252 AC: 1215 AN: 4812

European-Finnish (FIN) AF: 0.160 AC: 1693 AN: 10582

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.162 AC: 11007 AN: 67986

Other (OTH) AF: 0.195 AC: 412 AN: 2114

Alfa AF: 0.172 Hom.: 1364

Bravo AF: 0.199

Asia WGS AF: 0.273 AC: 945 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.7
DANN	Benign	0.60
PhyloP100		-0.31
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: rs9866277; hg19: chr3-86105340;