15-22858257-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030922.7(NIPA2):c.197-283A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 151,896 control chromosomes in the GnomAD database, including 16,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.42 (16706 hom., cov: 32)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.939

Genes affected

NIPA2 (HGNC:17044): (NIPA magnesium transporter 2) This gene encodes a possible magnesium transporter. This gene is located adjacent to the imprinted domain in the Prader-Willi syndrome deletion region of chromosome 15. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 3, 7 and 21.[provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 15-22858257-A-G is Benign according to our data. Variant chr15-22858257-A-G is described in ClinVar as [Benign]. Clinvar id is 1178664.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.706 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.197-283A>G		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.197-283A>G		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64331 AN: 151778 Hom.: 16667 Cov.: 32

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.267

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.383

Gnomad EAS AF: 0.654

Gnomad SAS AF: 0.381

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.262

Gnomad OTH AF: 0.427

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

GnomAD4 genome AF: 0.424 AC: 64427 AN: 151896 Hom.: 16706 Cov.: 32 AF XY: 0.425 AC XY: 31576 AN XY: 74218

Gnomad4 AFR AF: 0.713

Gnomad4 AMR AF: 0.445

Gnomad4 ASJ AF: 0.383

Gnomad4 EAS AF: 0.653

Gnomad4 SAS AF: 0.382

Gnomad4 FIN AF: 0.233

Gnomad4 NFE AF: 0.262

Gnomad4 OTH AF: 0.432

Alfa AF: 0.345 Hom.: 1332

Bravo AF: 0.449

Asia WGS AF: 0.545 AC: 1893 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	2.2
Dann	Benign	0.34

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: rs4778391; hg19: chr15-23014811;