3-85771266-A-G

Variant names:

• chr3-85771266-A-G
• rs7621179
• NM_001167675.2:c.89-30781A>G

Variant summary

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

The NM_001375960.1(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_001375960.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.324
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375960.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM2	NM_001167675.2	MANE Select	c.89-30781A>G		intron	N/A	NP_001161147.1
	CADM2	NM_001375960.1		c.89-30781A>G		intron	N/A	NP_001362889.1
	CADM2	NM_153184.4		c.68-30781A>G		intron	N/A	NP_694854.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM2	ENST00000383699.8	TSL:1 MANE Select	c.89-30781A>G		intron	N/A	ENSP00000373200.3
	CADM2	ENST00000405615.2	TSL:1	c.68-30781A>G		intron	N/A	ENSP00000384193.2
	CADM2	ENST00000407528.6	TSL:1	c.62-30781A>G		intron	N/A	ENSP00000384575.2

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

African (AFR) AF: 0.0850 AC: 3531 AN: 41520

American (AMR) AF: 0.0930 AC: 1421 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 166 AN: 3470

East Asian (EAS) AF: 0.188 AC: 973 AN: 5162

South Asian (SAS) AF: 0.109 AC: 524 AN: 4828

European-Finnish (FIN) AF: 0.0132 AC: 140 AN: 10620

Middle Eastern (MID) AF: 0.0377 AC: 11 AN: 292

European-Non Finnish (NFE) AF: 0.0177 AC: 1202 AN: 68004

Other (OTH) AF: 0.0473 AC: 100 AN: 2112

Alfa AF: 0.0337 Hom.: 117

Bravo AF: 0.0604

Asia WGS AF: 0.124 AC: 427 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.3
DANN	Benign	0.78
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: rs7621179; hg19: chr3-85820416;