Variant 21-21280658-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_004540.5(NCAM2):c.130+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,521,412 control chromosomes in the GnomAD database, including 43 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0032 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0018 ( 38 hom. )

Consequence

NCAM2
NM_004540.5 splice_region, intron

Scores

Splicing: ADA: 0.006744

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.08

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:

NCAM2 (HGNC:):

NCAM2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 21-21280658-T-C is Benign according to our data. Variant chr21-21280658-T-C is described in ClinVar as [Benign]. Clinvar id is 3044809.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00316 (482/152314) while in subpopulation EAS AF= 0.023 (119/5168). AF 95% confidence interval is 0.0197. There are 5 homozygotes in gnomad4. There are 341 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAM2	NM_004540.5 linkuse as main transcript	c.130+6T>C		splice_region_variant, intron_variant		ENST00000400546.6	NP_004531.2	O15394-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
NCAM2	ENST00000400546.6 linkuse as main transcript	c.130+6T>C	splice_region_variant, intron_variant	1	NM_004540.5	ENSP00000383392.1	O15394-1
NCAM2	ENST00000284894.8 linkuse as main transcript	c.76+6T>C	splice_region_variant, intron_variant	5		ENSP00000284894.8	H9KV31
NCAM2	ENST00000486367.1 linkuse as main transcript	n.145+6T>C	splice_region_variant, intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00317

AC:

483

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0230

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0287

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000470

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00482

AC:

928

AN:

192498

Hom.:

AF XY:

0.00463

AC XY:

490

AN XY:

105740

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000125

Gnomad EAS exome

AF:

0.0268

Gnomad SAS exome

AF:

0.000870

Gnomad FIN exome

AF:

0.0262

Gnomad NFE exome

AF:

0.000507

Gnomad OTH exome

AF:

0.00265

GnomAD4 exome

AF:

0.00177

AC:

2419

AN:

1369098

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

1149

AN XY:

678454

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000413

Gnomad4 EAS exome

AF:

0.0286

Gnomad4 SAS exome

AF:

0.00105

Gnomad4 FIN exome

AF:

0.0205

Gnomad4 NFE exome

AF:

0.000160

Gnomad4 OTH exome

AF:

0.00185

GnomAD4 genome

AF:

0.00316

AC:

482

AN:

152314

Hom.:

Cov.:

AF XY:

0.00458

AC XY:

341

AN XY:

74472

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0230

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.0287

Gnomad4 NFE

AF:

0.000470

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.000722

Hom.:

Bravo

AF:

0.00131

Asia WGS

AF:

0.00837

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

NCAM2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 02, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0067

dbscSNV1_RF

Benign

0.16

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