rs2826771

chr21-21291566-C-T

Variant summary

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

The NM_004540.5(NCAM2):c.482-538C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.169 in 151,478 control chromosomes in the GnomAD database, including 2,261 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 0.17 (2261 hom., cov: 32)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0590

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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM2	NM_004540.5	c.482-538C>T		intron_variant		ENST00000400546.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM2	ENST00000400546.6	c.482-538C>T		intron_variant		1	NM_004540.5	P1
NCAM2	ENST00000284894.8	c.428-538C>T		intron_variant		5
NCAM2	ENST00000461281.1	n.76-538C>T		intron_variant, non_coding_transcript_variant		3
NCAM2	ENST00000486367.1	n.497-538C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25602 AN: 151360 Hom.: 2257 Cov.: 32

Gnomad AFR AF: 0.131

Gnomad AMI AF: 0.0888

Gnomad AMR AF: 0.157

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.0762

Gnomad SAS AF: 0.156

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.186

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.169 AC: 25610 AN: 151478 Hom.: 2261 Cov.: 32 AF XY: 0.167 AC XY: 12333 AN XY: 74012

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.157

Gnomad4 ASJ AF: 0.138

Gnomad4 EAS AF: 0.0764

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.198

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.180

Alfa AF: 0.196 Hom.: 2081

Bravo AF: 0.164

Asia WGS AF: 0.0950 AC: 329 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	5.2
Dann	Benign	0.44

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: rs2826771; hg19: chr21-22663886;