rs2826891

Positions:

• chr21-21537795-C-T
• chr21-21537795-C-G
• chr21-21537795-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.2403-51C>T		intron_variant		ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.2403-51C>T		intron_variant		1	NM_004540.5	ENSP00000383392.1
NCAM2	ENST00000284894.8	c.2349-51C>T		intron_variant		5		ENSP00000284894.8

Frequencies

GnomAD3 genomes AF: 0.465 AC: 70525 AN: 151622 Hom.: 16783 Cov.: 32

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

GnomAD3 exomes AF: 0.434 AC: 71980 AN: 165902 Hom.: 16045 AF XY: 0.430 AC XY: 39071 AN XY: 90930

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 SAS exome AF: 0.311

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.: 10 AF XY: 0.451 AC XY: 179031 AN XY: 396826

Gnomad4 AFR exome AF: 0.507

Gnomad4 AMR exome AF: 0.486

Gnomad4 ASJ exome AF: 0.387

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.307

Gnomad4 FIN exome AF: 0.434

Gnomad4 NFE exome AF: 0.493

Gnomad4 OTH exome AF: 0.458

GnomAD4 genome AF: 0.465 AC: 70571 AN: 151740 Hom.: 16784 Cov.: 32 AF XY: 0.457 AC XY: 33857 AN XY: 74152

Gnomad4 AFR AF: 0.502

Gnomad4 AMR AF: 0.479

Gnomad4 ASJ AF: 0.389

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.412

Gnomad4 NFE AF: 0.486

Gnomad4 OTH AF: 0.470

Alfa AF: 0.446 Hom.: 13657

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
DANN	Benign	0.28

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

Other links and lift over

dbSNP: rs2826891; hg19: chr21-22910116;