Genetic Variant NM_004540.5:c.2403-51C>T (chr21-21537795-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004540.5(NCAM2):c.2403-51C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 905,186 control chromosomes in the GnomAD database, including 98,065 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.47 ( 16784 hom., cov: 32)

Exomes 𝑓: 0.46 ( 81281 hom. )

Consequence

NCAM2
NM_004540.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.342

Publications

12 publications found

Variant links:

Genes affected

NCAM2 (HGNC:7657): (neural cell adhesion molecule 2) The protein encoded by this gene belongs to the immunoglobulin superfamily. It is a type I membrane protein and may function in selective fasciculation and zone-to-zone projection of the primary olfactory axons. [provided by RefSeq, Jul 2008]

NCAM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.496 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM2	NM_004540.5 link	c.2403-51C>T		intron_variant	Intron 17 of 17	ENST00000400546.6	NP_004531.2	O15394-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6 link	c.2403-51C>T		intron_variant	Intron 17 of 17	1	NM_004540.5	ENSP00000383392.1		O15394-1
NCAM2	ENST00000284894.8 link	c.2349-51C>T		intron_variant	Intron 16 of 16	5		ENSP00000284894.8		H9KV31

Frequencies

GnomAD3 genomes

AF:

0.465

AC:

70525

AN:

151622

Hom.:

16783

Cov.:

show subpopulations

Gnomad AFR

AF:

0.502

Gnomad AMI

AF:

0.439

Gnomad AMR

AF:

0.480

Gnomad ASJ

AF:

0.389

Gnomad EAS

AF:

0.182

Gnomad SAS

AF:

0.288

Gnomad FIN

AF:

0.412

Gnomad MID

AF:

0.420

Gnomad NFE

AF:

0.486

Gnomad OTH

AF:

0.475

GnomAD2 exomes

AF:

0.434

AC:

71980

AN:

165902

AF XY:

0.430

show subpopulations

Gnomad AFR exome

AF:

0.506

Gnomad AMR exome

AF:

0.491

Gnomad ASJ exome

AF:

0.387

Gnomad EAS exome

AF:

0.194

Gnomad FIN exome

AF:

0.426

Gnomad NFE exome

AF:

0.478

Gnomad OTH exome

AF:

0.453

GnomAD4 exome

AF:

0.457

AC:

344254

AN:

753446

Hom.:

81281

Cov.:

AF XY:

0.451

AC XY:

179031

AN XY:

396826

show subpopulations

African (AFR)

AF:

0.507

AC:

8635

AN:

17020

American (AMR)

AF:

0.486

AC:

12165

AN:

25044

Ashkenazi Jewish (ASJ)

AF:

0.387

AC:

6693

AN:

17312

East Asian (EAS)

AF:

0.187

AC:

6365

AN:

34124

South Asian (SAS)

AF:

0.307

AC:

16897

AN:

55122

European-Finnish (FIN)

AF:

0.434

AC:

21344

AN:

49236

Middle Eastern (MID)

AF:

0.409

AC:

1114

AN:

2726

European-Non Finnish (NFE)

AF:

0.493

AC:

254661

AN:

517068

Other (OTH)

AF:

0.458

AC:

16380

AN:

35794

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

8849

17698

26548

35397

44246

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4840

9680

14520

19360

24200

<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:

0.465

AC:

70571

AN:

151740

Hom.:

16784

Cov.:

AF XY:

0.457

AC XY:

33857

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.502

AC:

20764

AN:

41366

American (AMR)

AF:

0.479

AC:

7310

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.389

AC:

1349

AN:

3472

East Asian (EAS)

AF:

0.182

AC:

937

AN:

5154

South Asian (SAS)

AF:

0.289

AC:

1388

AN:

4808

European-Finnish (FIN)

AF:

0.412

AC:

4332

AN:

10512

Middle Eastern (MID)

AF:

0.425

AC:

125

AN:

294

European-Non Finnish (NFE)

AF:

0.486

AC:

32977

AN:

67874

Other (OTH)

AF:

0.470

AC:

991

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1949

3898

5847

7796

9745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.458

Hom.:

23167

Bravo

AF:

0.474

Asia WGS

AF:

0.280

AC:

972

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

5.3

(source)

DANN

Benign

0.28

PhyloP100

0.34

Mutation Taster

=100/0

polymorphism (auto)

(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

Computational scores

Splicing

Publications

Other links and lift over