rs8132838

Positions:

• chr21-21075510-C-T

Variant summary

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

The NM_004540.5(NCAM2):​c.55+76892C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 151,990 control chromosomes in the GnomAD database, including 325 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 0.037 (325 hom., cov: 32)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.921

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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.123 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.55+76892C>T		intron_variant		ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.55+76892C>T		intron_variant		1	NM_004540.5	ENSP00000383392	P1

Frequencies

GnomAD3 genomes AF: 0.0370 AC: 5622 AN: 151874 Hom.: 322 Cov.: 32

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0186

Gnomad ASJ AF: 0.00635

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000750

Gnomad OTH AF: 0.0259

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

GnomAD4 genome AF: 0.0371 AC: 5636 AN: 151990 Hom.: 325 Cov.: 32 AF XY: 0.0357 AC XY: 2654 AN XY: 74308

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.0186

Gnomad4 ASJ AF: 0.00635

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000750

Gnomad4 OTH AF: 0.0257

Alfa AF: 0.0290 Hom.: 29

Bravo AF: 0.0417

Asia WGS AF: 0.00751 AC: 26 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	1.9
DANN	Benign	0.50

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: rs8132838; hg19: chr21-22447828;