rs2826851

Positions:

• chr21-21463626-A-G

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.1655-2980A>G		intron_variant		ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.1655-2980A>G		intron_variant		1	NM_004540.5	ENSP00000383392.1
NCAM2	ENST00000284894.8	c.1601-2980A>G		intron_variant		5		ENSP00000284894.8

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33990 AN: 151902 Hom.: 4374 Cov.: 32

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: 25 AN: 114 Hom.: 1 AF XY: 0.238 AC XY: 20 AN XY: 84

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.224 AC: 33978 AN: 152020 Hom.: 4372 Cov.: 32 AF XY: 0.219 AC XY: 16272 AN XY: 74284

Gnomad4 AFR AF: 0.130

Gnomad4 AMR AF: 0.207

Gnomad4 ASJ AF: 0.361

Gnomad4 EAS AF: 0.0232

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.259

Gnomad4 NFE AF: 0.291

Gnomad4 OTH AF: 0.261

Alfa AF: 0.260 Hom.: 695

Bravo AF: 0.216

Asia WGS AF: 0.0790 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.52

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: rs2826851; hg19: chr21-22835946;