rs2826728

Positions:

• chr21-21190327-G-A
• chr21-21190327-G-T

Variant summary

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

The NM_004540.5(NCAM2):​c.56-90251G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.799 in 152,140 control chromosomes in the GnomAD database, including 51,742 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 0.80 (51742 hom., cov: 32)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.268

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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.952 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.56-90251G>A		intron_variant		ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.56-90251G>A		intron_variant		1	NM_004540.5	ENSP00000383392.1

Frequencies

GnomAD3 genomes AF: 0.799 AC: 121484 AN: 152022 Hom.: 51733 Cov.: 32

Gnomad AFR AF: 0.488

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.820

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.951

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.958

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.799 AC: 121530 AN: 152140 Hom.: 51742 Cov.: 32 AF XY: 0.798 AC XY: 59389 AN XY: 74390

Gnomad4 AFR AF: 0.488

Gnomad4 AMR AF: 0.820

Gnomad4 ASJ AF: 0.965

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.827

Gnomad4 FIN AF: 0.951

Gnomad4 NFE AF: 0.958

Gnomad4 OTH AF: 0.827

Alfa AF: 0.925 Hom.: 75844

Bravo AF: 0.775

Asia WGS AF: 0.661 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.44
DANN	Benign	0.46

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: rs2826728; hg19: chr21-22562646;