15-22851955-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.139+85C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,127,056 control chromosomes in the GnomAD database, including 165,861 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (16792 hom., cov: 32)
  • Exomes 𝑓: 0.54 (149069 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.380

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=-0.83).
• BP6: Variant 15-22851955-C-T is Benign according to our data. Variant chr15-22851955-C-T is described in ClinVar as [Benign]. Clinvar id is 1245853.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.139+85C>T		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.139+85C>T		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66754 AN: 151902 Hom.: 16795 Cov.: 32

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.588

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.531

Gnomad FIN AF: 0.660

Gnomad MID AF: 0.372

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.544 AC: 530334 AN: 975036 Hom.: 149069 AF XY: 0.544 AC XY: 269824 AN XY: 495614

Gnomad4 AFR exome AF: 0.183

Gnomad4 AMR exome AF: 0.457

Gnomad4 ASJ exome AF: 0.397

Gnomad4 EAS exome AF: 0.266

Gnomad4 SAS exome AF: 0.537

Gnomad4 FIN exome AF: 0.656

Gnomad4 NFE exome AF: 0.573

Gnomad4 OTH exome AF: 0.507

GnomAD4 genome AF: 0.439 AC: 66746 AN: 152020 Hom.: 16792 Cov.: 32 AF XY: 0.442 AC XY: 32862 AN XY: 74296

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.394

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.530

Gnomad4 FIN AF: 0.660

Gnomad4 NFE AF: 0.563

Gnomad4 OTH AF: 0.428

Alfa AF: 0.527 Hom.: 44831

Bravo AF: 0.415

Asia WGS AF: 0.354 AC: 1229 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	-0.83
Cadd	Benign	6.8
Dann	Benign	0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs7170784; hg19: chr15-23021113; COSMIC: COSV61682718; COSMIC: COSV61682718;