rs11776272

Positions:

• chr8-22027033-A-G

Variant summary

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

The ENST00000518119.6(NPM2):​c.270+1261A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.269 in 152,184 control chromosomes in the GnomAD database, including 6,217 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 0.27 (6217 hom., cov: 31)
• Consequence: NPM2 ENST00000518119.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11

Genes affected

NPM2 (HGNC:7930): (nucleophosmin/nucleoplasmin 2) Predicted to enable RNA binding activity; chromatin binding activity; and histone binding activity. Involved in several processes, including blastocyst development; oocyte differentiation; and regulation of cell cycle process. Located in chromatin and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPM2	NM_001286680.2	c.270+1261A>G		intron_variant		ENST00000518119.6	NP_001273609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPM2	ENST00000518119.6	c.270+1261A>G		intron_variant		1	NM_001286680.2	ENSP00000427741	P2

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40883 AN: 152066 Hom.: 6221 Cov.: 31

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.296

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

GnomAD4 genome AF: 0.269 AC: 40891 AN: 152184 Hom.: 6217 Cov.: 31 AF XY: 0.263 AC XY: 19550 AN XY: 74414

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.228

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.296

Alfa AF: 0.340 Hom.: 11291

Bravo AF: 0.260

Asia WGS AF: 0.195 AC: 682 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
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: rs11776272; hg19: chr8-21884544;