3-85886263-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_001167675.2(CADM2):c.465C>T(p.Cys155=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00529 in 1,613,660 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (22 hom.)
• Consequence: CADM2 NM_001167675.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.473

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

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 3-85886263-C-T is Benign according to our data. Variant chr3-85886263-C-T is described in ClinVar as [Benign]. Clinvar id is 783311.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.473 with no splicing effect.
• BS2: High AC in GnomAd at 573 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM2	NM_001167675.2	c.465C>T	p.Cys155=	synonymous_variant	5/10	ENST00000383699.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM2	ENST00000383699.8	c.465C>T	p.Cys155=	synonymous_variant	5/10	1	NM_001167675.2	A1
CADM2	ENST00000405615.2	c.444C>T	p.Cys148=	synonymous_variant	4/10	1
CADM2	ENST00000407528.6	c.438C>T	p.Cys146=	synonymous_variant	4/10	1		P4

Frequencies

GnomAD3 genomes AF: 0.00377 AC: 573 AN: 151982 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000967

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000852

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00695

Gnomad OTH AF: 0.00766

GnomAD3 exomes AF: 0.00384 AC: 964 AN: 251172 Hom.: 3 AF XY: 0.00376 AC XY: 510 AN XY: 135744

Gnomad AFR exome AF: 0.000677

Gnomad AMR exome AF: 0.00202

Gnomad ASJ exome AF: 0.000894

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000196

Gnomad FIN exome AF: 0.00111

Gnomad NFE exome AF: 0.00721

Gnomad OTH exome AF: 0.00425

GnomAD4 exome AF: 0.00545 AC: 7961 AN: 1461558 Hom.: 22 Cov.: 31 AF XY: 0.00516 AC XY: 3752 AN XY: 727072

Gnomad4 AFR exome AF: 0.00105

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.000842

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000278

Gnomad4 FIN exome AF: 0.00120

Gnomad4 NFE exome AF: 0.00667

Gnomad4 OTH exome AF: 0.00459

GnomAD4 genome AF: 0.00377 AC: 573 AN: 152102 Hom.: 1 Cov.: 32 AF XY: 0.00346 AC XY: 257 AN XY: 74340

Gnomad4 AFR AF: 0.000964

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000852

Gnomad4 NFE AF: 0.00695

Gnomad4 OTH AF: 0.00758

Alfa AF: 0.00558 Hom.: 2

Bravo AF: 0.00388

EpiCase AF: 0.00688

EpiControl AF: 0.00593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 31, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	5.9
Dann	Benign	0.47

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

Other links and lift over

dbSNP: rs146378586; hg19: chr3-85935413; COSMIC: COSV67397108;