15-22865961-C-T

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.449-252C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 151,770 control chromosomes in the GnomAD database, including 16,429 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.43 (16429 hom., cov: 31)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.295

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=-0.92).
• BP6: Variant 15-22865961-C-T is Benign according to our data. Variant chr15-22865961-C-T is described in ClinVar as [Benign]. Clinvar id is 1280158.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.55 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.449-252C>T		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.449-252C>T		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 65993 AN: 151652 Hom.: 16432 Cov.: 31

Gnomad AFR AF: 0.190

Gnomad AMI AF: 0.590

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.393

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.655

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.429

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

GnomAD4 genome AF: 0.435 AC: 65987 AN: 151770 Hom.: 16429 Cov.: 31 AF XY: 0.438 AC XY: 32494 AN XY: 74146

Gnomad4 AFR AF: 0.189

Gnomad4 AMR AF: 0.440

Gnomad4 ASJ AF: 0.393

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.529

Gnomad4 FIN AF: 0.655

Gnomad4 NFE AF: 0.555

Gnomad4 OTH AF: 0.425

Alfa AF: 0.475 Hom.: 5944

Bravo AF: 0.411

Asia WGS AF: 0.352 AC: 1222 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

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.87
Dann	Benign	0.60

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: rs11263678; hg19: chr15-23007107;