chr21-21463626-A-G

Variant names:

• chr21-21463626-A-G
• rs2826851
• NM_004540.5:c.1655-2980A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004540.5(NCAM2):​c.1655-2980A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 152,134 control chromosomes in the GnomAD database, including 4,373 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 0.22 (4372 hom., cov: 32)
  • Exomes 𝑓: 0.22 (1 hom.)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.178
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.1655-2980A>G		intron_variant	Intron 12 of 17	ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.1655-2980A>G		intron_variant	Intron 12 of 17	1	NM_004540.5	ENSP00000383392.1
NCAM2	ENST00000284894.8	c.1601-2980A>G		intron_variant	Intron 11 of 16	5		ENSP00000284894.8
NCAM2	ENST00000484983.1	n.-115A>G		upstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 33990 AN: 151902 Hom.: 4374 Cov.: 32

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.207

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.0232

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.259

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.265

GnomAD4 exome AF: 0.219 AC: 25 AN: 114 Hom.: 1 AF XY: 0.238 AC XY: 20 AN XY: 84

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 2 AN: 4

East Asian (EAS) AF: 0.00 AC: 0 AN: 8

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 23 AN: 92

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.224 AC: 33978 AN: 152020 Hom.: 4372 Cov.: 32 AF XY: 0.219 AC XY: 16272 AN XY: 74284

African (AFR) AF: 0.130 AC: 5406 AN: 41496

American (AMR) AF: 0.207 AC: 3148 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1254 AN: 3472

East Asian (EAS) AF: 0.0232 AC: 120 AN: 5164

South Asian (SAS) AF: 0.146 AC: 703 AN: 4822

European-Finnish (FIN) AF: 0.259 AC: 2740 AN: 10570

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19809 AN: 67968

Other (OTH) AF: 0.261 AC: 550 AN: 2104

Alfa AF: 0.255 Hom.: 702

Bravo AF: 0.216

Asia WGS AF: 0.0790 AC: 279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.3
DANN	Benign	0.52
PhyloP100		-0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2826851; hg19: chr21-22835946;