chr3-85961477-C-T

Variant names:

• chr3-85961477-C-T
• rs762651968
• NM_001167675.2:c.800C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001167675.2(CADM2):​c.800C>T​(p.Pro267Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000694 in 1,441,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CADM2 NM_001167675.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.70
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23276907).

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.800C>T	p.Pro267Leu	missense	Exon 8 of 10	NP_001161147.1	Q8N3J6-2
	CADM2	NM_001375960.1		c.800C>T	p.Pro267Leu	missense	Exon 8 of 11	NP_001362889.1
	CADM2	NM_153184.4		c.779C>T	p.Pro260Leu	missense	Exon 7 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.800C>T	p.Pro267Leu	missense	Exon 8 of 10	ENSP00000373200.3	Q8N3J6-2
	CADM2	ENST00000405615.2	TSL:1	c.779C>T	p.Pro260Leu	missense	Exon 7 of 10	ENSP00000384193.2	Q8N3J6-3
	CADM2	ENST00000407528.6	TSL:1	c.773C>T	p.Pro258Leu	missense	Exon 7 of 10	ENSP00000384575.2	Q8N3J6-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.94e-7 AC: 1 AN: 1441068 Hom.: 0 Cov.: 31 AF XY: 0.00000140 AC XY: 1 AN XY: 715646

African (AFR) AF: 0.00 AC: 0 AN: 33110

American (AMR) AF: 0.00 AC: 0 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25534

East Asian (EAS) AF: 0.00 AC: 0 AN: 39322

South Asian (SAS) AF: 0.00 AC: 0 AN: 84006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52670

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.12e-7 AC: 1 AN: 1097090

Other (OTH) AF: 0.00 AC: 0 AN: 59380

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	Benign	0.28
BayesDel_addAF	Uncertain	0.043	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Benign	0.024	T
Eigen	Benign	-0.085
Eigen_PC	Benign	0.16
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.041	D
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Benign	-0.090	N
PhyloP100		5.7
PrimateAI	Pathogenic	0.80	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.22
Sift	Benign	0.25	T
Sift4G	Benign	0.33	T
Polyphen		0.071	B
Vest4		0.48
MutPred		0.67		Loss of disorder (P = 0.0139)
MVP		0.18
MPC		0.43
ClinPred		0.67	D
GERP RS		5.4
Varity_R		0.18
gMVP		0.82
Mutation Taster		=30/70	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

dbSNP: rs762651968; hg19: chr3-86010627; COSMIC: COSV105310781;