dbSNP rs1403998880: CADM2:p.Glu306Asp (chr3-85961595-A-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001167675.2(CADM2):c.918A>C(p.Glu306Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000249 in 1,606,728 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CADM2
NM_001167675.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.94

Variant links:

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]

CADM2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CADM2	NM_001167675.2 link	c.918A>C	p.Glu306Asp	missense_variant	Exon 8 of 10	ENST00000383699.8	NP_001161147.1	Q8N3J6-2G3XHN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CADM2	ENST00000383699.8 link	c.918A>C	p.Glu306Asp	missense_variant	Exon 8 of 10	1	NM_001167675.2	ENSP00000373200.3	Q8N3J6-2
CADM2	ENST00000405615.2 link	c.897A>C	p.Glu299Asp	missense_variant	Exon 7 of 10	1		ENSP00000384193.2	Q8N3J6-3
CADM2	ENST00000407528.6 link	c.891A>C	p.Glu297Asp	missense_variant	Exon 7 of 10	1		ENSP00000384575.2	Q8N3J6-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

151938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1454790

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723706

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000167

GnomAD4 genome

AF:

0.0000197

AC:

AN:

151938

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74178

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 08, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.897A>C (p.E299D) alteration is located in exon 7 (coding exon 7) of the CADM2 gene. This alteration results from a A to C substitution at nucleotide position 897, causing the glutamic acid (E) at amino acid position 299 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.51

BayesDel_addAF

Pathogenic

0.24

BayesDel_noAF

Uncertain

0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

.;T;.

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Uncertain

0.96

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.1

.;M;.

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.5

N;N;N

REVEL

Uncertain

0.46

Sift

Benign

0.037

D;D;D

Sift4G

Benign

0.38

T;T;T

Polyphen

0.99, 0.93

.;D;P

Vest4

0.85

MutPred

0.60

.;Gain of glycosylation at T293 (P = 0.0289);.;

MVP

0.77

MPC

0.94

ClinPred

0.86

GERP RS

5.5

Varity_R

0.33

gMVP

0.80

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over