3-86038921-C-A

Variant names:

• chr3-86038921-C-A
• rs17024414
• NM_001167675.2:c.971-26684C>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.971-26684C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0342 in 152,268 control chromosomes in the GnomAD database, including 176 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 0.034 (176 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.319
• Publications: 1 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.971-26684C>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.971-26684C>A		intron_variant	Intron 8 of 9	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000405615.2	c.1070-26684C>A		intron_variant	Intron 8 of 9	1		ENSP00000384193.2
CADM2	ENST00000407528.6	c.1064-26684C>A		intron_variant	Intron 8 of 9	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes AF: 0.0341 AC: 5185 AN: 152150 Hom.: 174 Cov.: 32

Gnomad AFR AF: 0.0832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0296

Gnomad ASJ AF: 0.00374

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.0215

Gnomad FIN AF: 0.0498

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00382

Gnomad OTH AF: 0.0291

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

GnomAD4 genome AF: 0.0342 AC: 5206 AN: 152268 Hom.: 176 Cov.: 32 AF XY: 0.0360 AC XY: 2680 AN XY: 74446

African (AFR) AF: 0.0835 AC: 3468 AN: 41534

American (AMR) AF: 0.0296 AC: 453 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00374 AC: 13 AN: 3472

East Asian (EAS) AF: 0.0615 AC: 317 AN: 5158

South Asian (SAS) AF: 0.0213 AC: 103 AN: 4830

European-Finnish (FIN) AF: 0.0498 AC: 529 AN: 10614

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00382 AC: 260 AN: 68034

Other (OTH) AF: 0.0288 AC: 61 AN: 2116

Alfa AF: 0.0250 Hom.: 15

Bravo AF: 0.0356

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.3
DANN	Benign	0.53
PhyloP100		-0.32
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: rs17024414; hg19: chr3-86088071;