3-86065615-T-C

Position:

• chr3-86065615-T-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.981T>C​(p.Ala327Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00441 in 1,612,896 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0045 (22 hom.)
• Consequence: CADM2 NM_001167675.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.398

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=-0.5).
• BP6: Variant 3-86065615-T-C is Benign according to our data. Variant chr3-86065615-T-C is described in ClinVar as [Benign]. Clinvar id is 771703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.398 with no splicing effect.
• BS2: High AC in GnomAd4 at 501 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CADM2	NM_001167675.2	c.981T>C	p.Ala327Ala	synonymous_variant	9/10	ENST00000383699.8	NP_001161147.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CADM2	ENST00000383699.8	c.981T>C	p.Ala327Ala	synonymous_variant	9/10	1	NM_001167675.2	ENSP00000373200.3
CADM2	ENST00000405615.2	c.1080T>C	p.Ala360Ala	synonymous_variant	9/10	1		ENSP00000384193.2
CADM2	ENST00000407528.6	c.1074T>C	p.Ala358Ala	synonymous_variant	9/10	1		ENSP00000384575.2

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 501 AN: 152248 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.00360

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00503

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00341 AC: 851 AN: 249658 Hom.: 5 AF XY: 0.00326 AC XY: 440 AN XY: 134962

Gnomad AFR exome AF: 0.00130

Gnomad AMR exome AF: 0.00354

Gnomad ASJ exome AF: 0.00210

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000330

Gnomad FIN exome AF: 0.000509

Gnomad NFE exome AF: 0.00575

Gnomad OTH exome AF: 0.00429

GnomAD4 exome AF: 0.00453 AC: 6610 AN: 1460530 Hom.: 22 Cov.: 30 AF XY: 0.00447 AC XY: 3248 AN XY: 726554

Gnomad4 AFR exome AF: 0.000988

Gnomad4 AMR exome AF: 0.00324

Gnomad4 ASJ exome AF: 0.00203

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000698

Gnomad4 FIN exome AF: 0.00109

Gnomad4 NFE exome AF: 0.00548

Gnomad4 OTH exome AF: 0.00351

GnomAD4 genome AF: 0.00329 AC: 501 AN: 152366 Hom.: 2 Cov.: 32 AF XY: 0.00309 AC XY: 230 AN XY: 74502

Gnomad4 AFR AF: 0.00120

Gnomad4 AMR AF: 0.00359

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00503

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00217 Hom.: 1

Bravo AF: 0.00359

EpiCase AF: 0.00688

EpiControl AF: 0.00708

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

Labcorp Genetics (formerly Invitae), Labcorp

Jul 10, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	8.7
DANN	Benign	0.64

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: rs139890320; hg19: chr3-86114765;