chr21-21176833-A-G

Variant names:

• chr21-21176833-A-G
• rs2155798
• NM_004540.5:c.56-103745A>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.56-103745A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.8 in 151,562 control chromosomes in the GnomAD database, including 51,595 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 (51595 hom., cov: 30)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.41
• Publications: 1 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=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.951 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCAM2	NM_004540.5	c.56-103745A>G		intron_variant	Intron 1 of 17	ENST00000400546.6	NP_004531.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCAM2	ENST00000400546.6	c.56-103745A>G		intron_variant	Intron 1 of 17	1	NM_004540.5	ENSP00000383392.1

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121264 AN: 151442 Hom.: 51593 Cov.: 30

Gnomad AFR AF: 0.501

Gnomad AMI AF: 0.981

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.956

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.952

Gnomad MID AF: 0.862

Gnomad NFE AF: 0.957

Gnomad OTH AF: 0.830

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

GnomAD4 genome AF: 0.800 AC: 121301 AN: 151562 Hom.: 51595 Cov.: 30 AF XY: 0.799 AC XY: 59176 AN XY: 74046

African (AFR) AF: 0.501 AC: 20721 AN: 41370

American (AMR) AF: 0.819 AC: 12457 AN: 15204

Ashkenazi Jewish (ASJ) AF: 0.956 AC: 3314 AN: 3466

East Asian (EAS) AF: 0.613 AC: 3161 AN: 5158

South Asian (SAS) AF: 0.820 AC: 3934 AN: 4798

European-Finnish (FIN) AF: 0.952 AC: 9964 AN: 10468

Middle Eastern (MID) AF: 0.862 AC: 250 AN: 290

European-Non Finnish (NFE) AF: 0.957 AC: 64864 AN: 67788

Other (OTH) AF: 0.826 AC: 1741 AN: 2108

Alfa AF: 0.852 Hom.: 23852

Bravo AF: 0.778

Asia WGS AF: 0.661 AC: 2273 AN: 3440

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.3
DANN	Benign	0.73
PhyloP100		1.4
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: rs2155798; hg19: chr21-22549151;