NM_004540.5:c.56-134799G>A

Variant names:

• chr21-21145779-G-A
• rs12483298
• NM_004540.5:c.56-134799G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004540.5(NCAM2):​c.56-134799G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.248 in 152,022 control chromosomes in the GnomAD database, including 5,216 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 0.25 (5216 hom., cov: 33)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.112
• Publications: 0 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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.439 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.56-134799G>A		intron_variant	Intron 1 of 17	ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.56-134799G>A		intron_variant	Intron 1 of 17	1	NM_004540.5	ENSP00000383392.1

Frequencies

GnomAD3 genomes AF: 0.248 AC: 37682 AN: 151902 Hom.: 5214 Cov.: 33

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.281

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.361

Gnomad FIN AF: 0.290

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.270

Gnomad OTH AF: 0.277

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

GnomAD4 genome AF: 0.248 AC: 37679 AN: 152022 Hom.: 5216 Cov.: 33 AF XY: 0.255 AC XY: 18940 AN XY: 74300

African (AFR) AF: 0.139 AC: 5754 AN: 41486

American (AMR) AF: 0.281 AC: 4291 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1083 AN: 3468

East Asian (EAS) AF: 0.454 AC: 2351 AN: 5178

South Asian (SAS) AF: 0.360 AC: 1735 AN: 4818

European-Finnish (FIN) AF: 0.290 AC: 3065 AN: 10554

Middle Eastern (MID) AF: 0.320 AC: 94 AN: 294

European-Non Finnish (NFE) AF: 0.270 AC: 18345 AN: 67938

Other (OTH) AF: 0.273 AC: 576 AN: 2110

Alfa AF: 0.263 Hom.: 22171

Bravo AF: 0.241

Asia WGS AF: 0.367 AC: 1278 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.56
PhyloP100		-0.11
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: rs12483298; hg19: chr21-22518097;