3-86065684-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001167675.2(CADM2):c.1050G>C(p.Thr350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00777 in 1,613,940 control chromosomes in the GnomAD database, including 66 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0055 (5 hom., cov: 32)
  • Exomes 𝑓: 0.0080 (61 hom.)
• Consequence: CADM2 NM_001167675.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.07

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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 3-86065684-G-C is Benign according to our data. Variant chr3-86065684-G-C is described in ClinVar as [Benign]. Clinvar id is 788972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.07 with no splicing effect.
• BS2: High AC in GnomAd at 843 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CADM2	NM_001167675.2	c.1050G>C	p.Thr350=	synonymous_variant	9/10	ENST00000383699.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CADM2	ENST00000383699.8	c.1050G>C	p.Thr350=	synonymous_variant	9/10	1	NM_001167675.2	A1
CADM2	ENST00000405615.2	c.1149G>C	p.Thr383=	synonymous_variant	9/10	1
CADM2	ENST00000407528.6	c.1143G>C	p.Thr381=	synonymous_variant	9/10	1		P4

Frequencies

GnomAD3 genomes AF: 0.00554 AC: 843 AN: 152174 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00543

Gnomad ASJ AF: 0.0187

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00558

Gnomad FIN AF: 0.000566

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00850

Gnomad OTH AF: 0.00812

GnomAD3 exomes AF: 0.00570 AC: 1432 AN: 251132 Hom.: 6 AF XY: 0.00607 AC XY: 824 AN XY: 135734

Gnomad AFR exome AF: 0.00154

Gnomad AMR exome AF: 0.00512

Gnomad ASJ exome AF: 0.0168

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00526

Gnomad FIN exome AF: 0.000370

Gnomad NFE exome AF: 0.00753

Gnomad OTH exome AF: 0.00605

GnomAD4 exome AF: 0.00800 AC: 11697 AN: 1461648 Hom.: 61 Cov.: 30 AF XY: 0.00791 AC XY: 5752 AN XY: 727124

Gnomad4 AFR exome AF: 0.000926

Gnomad4 AMR exome AF: 0.00512

Gnomad4 ASJ exome AF: 0.0157

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00535

Gnomad4 FIN exome AF: 0.000524

Gnomad4 NFE exome AF: 0.00908

Gnomad4 OTH exome AF: 0.00712

GnomAD4 genome AF: 0.00553 AC: 842 AN: 152292 Hom.: 5 Cov.: 32 AF XY: 0.00471 AC XY: 351 AN XY: 74454

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00542

Gnomad4 ASJ AF: 0.0187

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00538

Gnomad4 FIN AF: 0.000566

Gnomad4 NFE AF: 0.00850

Gnomad4 OTH AF: 0.00803

Alfa AF: 0.00621 Hom.: 1

Bravo AF: 0.00569

Asia WGS AF: 0.00231 AC: 8 AN: 3478

EpiCase AF: 0.00862

EpiControl AF: 0.00730

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

May 24, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
Cadd	Benign	0.11
Dann	Benign	0.70

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: rs36050101; hg19: chr3-86114834;