Variant 21-21335569-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004540.5(NCAM2):c.802G>A(p.Val268Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,459,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

NCAM2
NM_004540.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.06

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045354992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM2	NM_004540.5 linkuse as main transcript	c.802G>A	p.Val268Ile	missense_variant	7/18	ENST00000400546.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM2	ENST00000400546.6 linkuse as main transcript	c.802G>A	p.Val268Ile	missense_variant	7/18	1	NM_004540.5	P1	O15394-1
NCAM2	ENST00000284894.8 linkuse as main transcript	c.748G>A	p.Val250Ile	missense_variant	6/17	5
NCAM2	ENST00000461281.1 linkuse as main transcript	n.396G>A		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000568

AC:

AN:

246396

Hom.:

AF XY:

0.0000374

AC XY:

AN XY:

133844

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000415

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000123

AC:

AN:

1459210

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725964

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.000338

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000302

ExAC

AF:

0.0000497

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 30, 2022

The c.802G>A (p.V268I) alteration is located in exon 7 (coding exon 7) of the NCAM2 gene. This alteration results from a G to A substitution at nucleotide position 802, causing the valine (V) at amino acid position 268 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.080

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.53

Cadd

Benign

Dann

Benign

0.087

DEOGEN2

Benign

0.055

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.80

T;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Benign

0.43

PROVEAN

Benign

0.36

N;.

REVEL

Benign

0.079

Sift

Benign

1.0

T;.

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;.

Vest4

0.15

MutPred

0.42

Gain of phosphorylation at T267 (P = 0.2635);.;

MVP

0.22

MPC

0.059

ClinPred

0.039

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.064

gMVP

0.22

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over