dbSNP rs2826851: NCAM2:c.1655-2980A>G (chr21-21463626-A-G) – 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.1655-2980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,134 control chromosomes in the GnomAD database, including 4,373 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 0.22 ( 4372 hom., cov: 32)

Exomes 𝑓: 0.22 ( 1 hom. )

Consequence

NCAM2
NM_004540.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.178

Publications

4 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=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 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.1655-2980A>G	intron	N/A	NP_004531.2
NCAM2	NM_001352592.2		c.1730-2980A>G	intron	N/A	NP_001339521.1
NCAM2	NM_001352591.2		c.1655-2980A>G	intron	N/A	NP_001339520.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCAM2	ENST00000400546.6	TSL:1 MANE Select	c.1655-2980A>G	intron	N/A	ENSP00000383392.1	O15394-1
NCAM2	ENST00000284894.8	TSL:5	c.1601-2980A>G	intron	N/A	ENSP00000284894.8	H9KV31
NCAM2	ENST00000484983.1	TSL:3	n.-115A>G	upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

33990

AN:

151902

Hom.:

4374

Cov.:

show subpopulations

Gnomad AFR

AF:

0.130

Gnomad AMI

AF:

0.150

Gnomad AMR

AF:

0.207

Gnomad ASJ

AF:

0.361

Gnomad EAS

AF:

0.0232

Gnomad SAS

AF:

0.146

Gnomad FIN

AF:

0.259

Gnomad MID

AF:

0.386

Gnomad NFE

AF:

0.292

Gnomad OTH

AF:

0.265

GnomAD4 exome

AF:

0.219

AC:

AN:

114

Hom.:

AF XY:

0.238

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.224

AC:

33978

AN:

152020

Hom.:

4372

Cov.:

AF XY:

0.219

AC XY:

16272

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.130

AC:

5406

AN:

41496

American (AMR)

AF:

0.207

AC:

3148

AN:

15218

Ashkenazi Jewish (ASJ)

AF:

0.361

AC:

1254

AN:

3472

East Asian (EAS)

AF:

0.0232

AC:

120

AN:

5164

South Asian (SAS)

AF:

0.146

AC:

703

AN:

4822

European-Finnish (FIN)

AF:

0.259

AC:

2740

AN:

10570

Middle Eastern (MID)

AF:

0.378

AC:

111

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19809

AN:

67968

Other (OTH)

AF:

0.261

AC:

550

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1292

2584

3876

5168

6460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

358

716

1074

1432

1790

<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:

0.255

Hom.:

702

Bravo

AF:

0.216

Asia WGS

AF:

0.0790

AC:

279

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.3

(source)

DANN

Benign

0.52

PhyloP100

-0.18

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over