chr3-85758440-T-G

Variant names:

• chr3-85758440-T-G
• rs13078960
• NM_001167675.2:c.88+31892T>G

Variant summary

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

The NM_001167675.2(CADM2):​c.88+31892T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,080 control chromosomes in the GnomAD database, including 2,027 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 0.15 (2027 hom., cov: 32)
• Consequence: CADM2 NM_001167675.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 82 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.197 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.88+31892T>G		intron_variant	Intron 2 of 9	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.88+31892T>G		intron_variant	Intron 2 of 9	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000405615.2	c.67+31892T>G		intron_variant	Intron 1 of 9	1		ENSP00000384193.2
CADM2	ENST00000407528.6	c.62-43607T>G		intron_variant	Intron 1 of 9	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes AF: 0.145 AC: 22088 AN: 151962 Hom.: 2030 Cov.: 32

Gnomad AFR AF: 0.0616

Gnomad AMI AF: 0.197

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.00462

Gnomad SAS AF: 0.0961

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.173

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

GnomAD4 genome AF: 0.145 AC: 22075 AN: 152080 Hom.: 2027 Cov.: 32 AF XY: 0.140 AC XY: 10414 AN XY: 74336

African (AFR) AF: 0.0614 AC: 2550 AN: 41552

American (AMR) AF: 0.130 AC: 1984 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1067 AN: 3460

East Asian (EAS) AF: 0.00463 AC: 24 AN: 5180

South Asian (SAS) AF: 0.0959 AC: 463 AN: 4826

European-Finnish (FIN) AF: 0.169 AC: 1792 AN: 10578

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13606 AN: 67928

Other (OTH) AF: 0.171 AC: 360 AN: 2106

Alfa AF: 0.184 Hom.: 4702

Bravo AF: 0.139

Asia WGS AF: 0.0570 AC: 199 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.52
PhyloP100		0.12
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: rs13078960; hg19: chr3-85807590;