3-85802161-C-T

Position:

• chr3-85802161-C-T

Variant summary

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

The NM_001167675.2(CADM2):​c.203C>T​(p.Pro68Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CADM2 NM_001167675.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.50

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-AS2 (HGNC:41247): (CADM2 antisense RNA 2)

ACMG classification

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/exons	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.203C>T	p.Pro68Leu	missense_variant	3/10	ENST00000383699.8	NP_001161147.1
CADM2-AS2	NR_046752.1	n.183-1210G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.203C>T	p.Pro68Leu	missense_variant	3/10	1	NM_001167675.2	ENSP00000373200	A1
CADM2	ENST00000405615.2	c.182C>T	p.Pro61Leu	missense_variant	2/10	1		ENSP00000384193
CADM2	ENST00000407528.6	c.176C>T	p.Pro59Leu	missense_variant	2/10	1		ENSP00000384575	P4
CADM2-AS2	ENST00000467225.1	n.183-1210G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 14, 2024

The c.182C>T (p.P61L) alteration is located in exon 2 (coding exon 2) of the CADM2 gene. This alteration results from a C to T substitution at nucleotide position 182, causing the proline (P) at amino acid position 61 to be replaced by a leucine (L). 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	Pathogenic	0.88
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.27	.;T;.
Eigen	Pathogenic	0.82
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Uncertain	0.90	D
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.67	D;D;D
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.7	.;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.8	D;D;D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D;D;D
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	.;D;D
Vest4		0.61
MutPred		0.57		.;Loss of catalytic residue at P59 (P = 0.0025);.;
MVP		0.56
MPC		1.1
ClinPred		1.0	D
GERP RS		5.3
Varity_R		0.69
gMVP		0.78

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.

Other links and lift over

hg19: chr3-85851311;