rs232378

chr21-21348119-T-Achr21-21348119-T-C

Variant summary

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

The NM_004540.5(NCAM2):c.1044+9585T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,764 control chromosomes in the GnomAD database, including 14,458 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 0.43 (14458 hom., cov: 32)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.15

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=-1.02).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM2	NM_004540.5	c.1044+9585T>A		intron_variant		ENST00000400546.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM2	ENST00000400546.6	c.1044+9585T>A		intron_variant		1	NM_004540.5	P1
NCAM2	ENST00000284894.8	c.990+9585T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65735 AN: 151650 Hom.: 14453 Cov.: 32

Gnomad AFR AF: 0.384

Gnomad AMI AF: 0.678

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.586

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.425

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

GnomAD4 genome AF: 0.433 AC: 65779 AN: 151764 Hom.: 14458 Cov.: 32 AF XY: 0.431 AC XY: 31955 AN XY: 74134

Gnomad4 AFR AF: 0.384

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.466

Gnomad4 OTH AF: 0.427

Alfa AF: 0.458 Hom.: 1986

Bravo AF: 0.428

Asia WGS AF: 0.470 AC: 1635 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.46
Dann	Benign	0.16

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: rs232378; hg19: chr21-22720439;