NM_001286680.2:c.270+1261A>G

Variant names:

• chr8-22027033-A-G
• rs11776272
• NM_001286680.2:c.270+1261A>G

Variant summary

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

The NM_001286680.2(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 NM_001286680.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.11
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
NPM2	NM_001286680.2	c.270+1261A>G		intron_variant	Intron 5 of 9	ENST00000518119.6	NP_001273609.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NPM2	ENST00000518119.6	c.270+1261A>G		intron_variant	Intron 5 of 9	1	NM_001286680.2	ENSP00000427741.1

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

African (AFR) AF: 0.157 AC: 6525 AN: 41516

American (AMR) AF: 0.228 AC: 3485 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1400 AN: 3466

East Asian (EAS) AF: 0.144 AC: 745 AN: 5188

South Asian (SAS) AF: 0.183 AC: 883 AN: 4818

European-Finnish (FIN) AF: 0.312 AC: 3300 AN: 10592

Middle Eastern (MID) AF: 0.374 AC: 110 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23538 AN: 68006

Other (OTH) AF: 0.296 AC: 624 AN: 2110

Alfa AF: 0.321 Hom.: 25561

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
PhyloP100		1.1
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: rs11776272; hg19: chr8-21884544;