chr21-21138436-A-G

Position:

• chr21-21138436-A-G

Variant summary

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

The NM_004540.5(NCAM2):​c.55+139818A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.362 in 151,592 control chromosomes in the GnomAD database, including 9,936 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 0.36 (9936 hom., cov: 32)
• Consequence: NCAM2 NM_004540.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.198

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.402 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCAM2	NM_004540.5	c.55+139818A>G		intron_variant		ENST00000400546.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCAM2	ENST00000400546.6	c.55+139818A>G		intron_variant		1	NM_004540.5	P1

Frequencies

GnomAD3 genomes AF: 0.362 AC: 54859 AN: 151474 Hom.: 9932 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.331

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.328

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.355

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

GnomAD4 genome AF: 0.362 AC: 54899 AN: 151592 Hom.: 9936 Cov.: 32 AF XY: 0.357 AC XY: 26422 AN XY: 74060

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.331

Gnomad4 ASJ AF: 0.390

Gnomad4 EAS AF: 0.417

Gnomad4 SAS AF: 0.330

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.357

Alfa AF: 0.368 Hom.: 1427

Bravo AF: 0.363

Asia WGS AF: 0.372 AC: 1289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.5
DANN	Benign	0.31

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: rs2826689; hg19: chr21-22510754;