NM_004540.5:c.482-538C>T

Variant names:

• chr21-21291566-C-T
• rs2826771
• NM_004540.5:c.482-538C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004540.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM2	NM_004540.5	MANE Select	c.482-538C>T		intron	N/A	NP_004531.2
	NCAM2	NM_001352592.2		c.557-538C>T		intron	N/A	NP_001339521.1
	NCAM2	NM_001352591.2		c.482-538C>T		intron	N/A	NP_001339520.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCAM2	ENST00000400546.6	TSL:1 MANE Select	c.482-538C>T		intron	N/A	ENSP00000383392.1
	NCAM2	ENST00000284894.8	TSL:5	c.428-538C>T		intron	N/A	ENSP00000284894.8
	NCAM2	ENST00000461281.1	TSL:3	n.76-538C>T		intron	N/A

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

African (AFR) AF: 0.131 AC: 5423 AN: 41354

American (AMR) AF: 0.157 AC: 2376 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3466

East Asian (EAS) AF: 0.0764 AC: 392 AN: 5134

South Asian (SAS) AF: 0.157 AC: 752 AN: 4792

European-Finnish (FIN) AF: 0.198 AC: 2083 AN: 10500

Middle Eastern (MID) AF: 0.186 AC: 54 AN: 290

European-Non Finnish (NFE) AF: 0.201 AC: 13590 AN: 67754

Other (OTH) AF: 0.180 AC: 379 AN: 2100

Alfa AF: 0.195 Hom.: 2393

Bravo AF: 0.164

Asia WGS AF: 0.0950 AC: 329 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.2
DANN	Benign	0.44
PhyloP100		-0.059
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2826771; hg19: chr21-22663886;