Genetic Variant CADM2:p.Ala327Ala (chr3-86065615-T-C) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.398

Publications

1 publications found

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
CADM2	NM_001167675.2 link	c.981T>C	p.Ala327Ala	synonymous_variant	Exon 9 of 10	ENST00000383699.8	NP_001161147.1	Q8N3J6-2G3XHN4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CADM2	ENST00000383699.8 link	c.981T>C	p.Ala327Ala	synonymous_variant	Exon 9 of 10	1	NM_001167675.2	ENSP00000373200.3	Q8N3J6-2
CADM2	ENST00000405615.2 link	c.1080T>C	p.Ala360Ala	synonymous_variant	Exon 9 of 10	1		ENSP00000384193.2	Q8N3J6-3
CADM2	ENST00000407528.6 link	c.1074T>C	p.Ala358Ala	synonymous_variant	Exon 9 of 10	1		ENSP00000384575.2	Q8N3J6-1

Frequencies

GnomAD3 genomes

AF:

0.00329

AC:

501

AN:

152248

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00341

AC:

851

AN:

249658

AF XY:

0.00326

show subpopulations

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 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.:

Cov.:

AF XY:

0.00447

AC XY:

3248

AN XY:

726554

show subpopulations

African (AFR)

AF:

0.000988

AC:

AN:

33404

American (AMR)

AF:

0.00324

AC:

144

AN:

44442

Ashkenazi Jewish (ASJ)

AF:

0.00203

AC:

AN:

26060

East Asian (EAS)

AF:

0.00

AC:

AN:

39612

South Asian (SAS)

AF:

0.0000698

AC:

AN:

86008

European-Finnish (FIN)

AF:

0.00109

AC:

AN:

53390

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00548

AC:

6093

AN:

1111532

Other (OTH)

AF:

0.00351

AC:

212

AN:

60326

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

295

590

885

1180

1475

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

234

468

702

936

1170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00329

AC:

501

AN:

152366

Hom.:

Cov.:

AF XY:

0.00309

AC XY:

230

AN XY:

74502

show subpopulations

African (AFR)

AF:

0.00120

AC:

AN:

41600

American (AMR)

AF:

0.00359

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00503

AC:

342

AN:

68038

Other (OTH)

AF:

0.00378

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00217

Hom.:

Bravo

AF:

0.00359

EpiCase

AF:

0.00688

EpiControl

AF:

0.00708

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 10, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

8.7

(source)

DANN

Benign

0.64

PhyloP100

0.40

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over