21-21145779-G-A

Position:

• chr21-21145779-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.84).
• 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/exons	MANE	UniProt
NCAM2	NM_004540.5	c.56-134799G>A		intron_variant		ENST00000400546.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM2	ENST00000400546.6	c.56-134799G>A		intron_variant		1	NM_004540.5	P1

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

Gnomad4 AFR AF: 0.139

Gnomad4 AMR AF: 0.281

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.360

Gnomad4 FIN AF: 0.290

Gnomad4 NFE AF: 0.270

Gnomad4 OTH AF: 0.273

Alfa AF: 0.267 Hom.: 10617

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

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: rs12483298; hg19: chr21-22518097;