rs11088859

chr21-21317024-G-Achr21-21317024-G-C

Variant summary

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

The NM_004540.5(NCAM2):c.620-7359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 152,092 control chromosomes in the GnomAD database, including 293 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 0.046 (293 hom., cov: 32)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00600

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM2	NM_004540.5	c.620-7359G>A		intron_variant		ENST00000400546.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM2	ENST00000400546.6	c.620-7359G>A		intron_variant		1	NM_004540.5	P1
NCAM2	ENST00000284894.8	c.566-7359G>A		intron_variant		5
NCAM2	ENST00000461281.1	n.214-7359G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0459 AC: 6982 AN: 151974 Hom.: 292 Cov.: 32

Gnomad AFR AF: 0.0835

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.0327

Gnomad FIN AF: 0.0374

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0165

Gnomad OTH AF: 0.0331

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

GnomAD4 genome AF: 0.0459 AC: 6985 AN: 152092 Hom.: 293 Cov.: 32 AF XY: 0.0471 AC XY: 3502 AN XY: 74344

Gnomad4 AFR AF: 0.0834

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0374

Gnomad4 NFE AF: 0.0165

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.0253 Hom.: 228

Bravo AF: 0.0487

Asia WGS AF: 0.107 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	2.6
Dann	Benign	0.37

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: rs11088859; hg19: chr21-22689344;