3-85802161-C-T

Variant names:

• chr3-85802161-C-T
• NM_001167675.2:c.203C>T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001167675.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM2	NM_001167675.2	MANE Select	c.203C>T	p.Pro68Leu	missense	Exon 3 of 10	NP_001161147.1	Q8N3J6-2
	CADM2	NM_001375960.1		c.203C>T	p.Pro68Leu	missense	Exon 3 of 11	NP_001362889.1
	CADM2	NM_153184.4		c.182C>T	p.Pro61Leu	missense	Exon 2 of 10	NP_694854.2	Q8N3J6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CADM2	ENST00000383699.8	TSL:1 MANE Select	c.203C>T	p.Pro68Leu	missense	Exon 3 of 10	ENSP00000373200.3	Q8N3J6-2
	CADM2	ENST00000405615.2	TSL:1	c.182C>T	p.Pro61Leu	missense	Exon 2 of 10	ENSP00000384193.2	Q8N3J6-3
	CADM2	ENST00000407528.6	TSL:1	c.176C>T	p.Pro59Leu	missense	Exon 2 of 10	ENSP00000384575.2	Q8N3J6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Uncertain	-0.15	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		1.0	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
Mutation Taster		=21/79	disease causing

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

hg19: chr3-85851311;