Variant 3-85935770-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001167675.2(CADM2):c.704C>A(p.Thr235Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CADM2
NM_001167675.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.86

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.33830196).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM2	NM_001167675.2 linkuse as main transcript	c.704C>A	p.Thr235Lys	missense_variant	7/10	ENST00000383699.8	NP_001161147.1	Q8N3J6-2G3XHN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CADM2	ENST00000383699.8 linkuse as main transcript	c.704C>A	p.Thr235Lys	missense_variant	7/10	1	NM_001167675.2	ENSP00000373200.3	Q8N3J6-2
CADM2	ENST00000405615.2 linkuse as main transcript	c.683C>A	p.Thr228Lys	missense_variant	6/10	1		ENSP00000384193.2	Q8N3J6-3
CADM2	ENST00000407528.6 linkuse as main transcript	c.677C>A	p.Thr226Lys	missense_variant	6/10	1		ENSP00000384575.2	Q8N3J6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1408040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

702740

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 01, 2024

The c.683C>A (p.T228K) alteration is located in exon 6 (coding exon 6) of the CADM2 gene. This alteration results from a C to A substitution at nucleotide position 683, causing the threonine (T) at amino acid position 228 to be replaced by a lysine (K). 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

Benign

0.14

BayesDel_addAF

Pathogenic

0.20

BayesDel_noAF

Uncertain

0.050

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.011

.;T;.

Eigen

Benign

-0.073

Eigen_PC

Benign

0.16

FATHMM_MKL

Uncertain

0.95

M_CAP

Benign

0.033

MetaRNN

Benign

0.34

T;T;T

MetaSVM

Benign

-0.68

MutationAssessor

Benign

0.27

.;N;.

PrimateAI

Uncertain

0.71

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.89

T;T;T

Sift4G

Benign

0.75

T;T;T

Polyphen

0.0070, 0.046

.;B;B

Vest4

0.70

MutPred

0.51

.;Gain of methylation at T226 (P = 0.0095);.;

MVP

0.49

MPC

0.51

ClinPred

0.72

GERP RS

5.7

Varity_R

0.25

gMVP

0.90

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over