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:

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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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004540.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
NCAM2	NM_004540.5	MANE Select	c.2403-51C>T	intron	N/A	NP_004531.2
NCAM2	NM_001352592.2		c.2478-51C>T	intron	N/A	NP_001339521.1
NCAM2	NM_001352591.2		c.2439-51C>T	intron	N/A	NP_001339520.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM2	ENST00000400546.6	TSL:1 MANE Select	c.2403-51C>T		intron	N/A	ENSP00000383392.1	O15394-1
	NCAM2	ENST00000284894.8	TSL:5	c.2349-51C>T		intron	N/A	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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over