15-22853374-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_030922.7(NIPA2):c.196+123del variant causes a intron change. The variant allele was found at a frequency of 0.154 in 377,258 control chromosomes in the GnomAD database, including 197 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.050 (171 hom., cov: 23)
  • Exomes 𝑓: 0.21 (26 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.79

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 -10 ACMG points.

• BP6: Variant 15-22853374-CT-C is Benign according to our data. Variant chr15-22853374-CT-C is described in ClinVar as [Benign]. Clinvar id is 1245041.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.196+123del		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.196+123del		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.0499 AC: 6848 AN: 137100 Hom.: 172 Cov.: 23

Gnomad AFR AF: 0.0478

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.0440

Gnomad ASJ AF: 0.0832

Gnomad EAS AF: 0.217

Gnomad SAS AF: 0.0525

Gnomad FIN AF: 0.0257

Gnomad MID AF: 0.0925

Gnomad NFE AF: 0.0416

Gnomad OTH AF: 0.0489

GnomAD4 exome AF: 0.214 AC: 51391 AN: 240134 Hom.: 26 AF XY: 0.214 AC XY: 27784 AN XY: 129764

Gnomad4 AFR exome AF: 0.209

Gnomad4 AMR exome AF: 0.182

Gnomad4 ASJ exome AF: 0.217

Gnomad4 EAS exome AF: 0.297

Gnomad4 SAS exome AF: 0.216

Gnomad4 FIN exome AF: 0.200

Gnomad4 NFE exome AF: 0.209

Gnomad4 OTH exome AF: 0.215

GnomAD4 genome AF: 0.0500 AC: 6850 AN: 137124 Hom.: 171 Cov.: 23 AF XY: 0.0512 AC XY: 3374 AN XY: 65946

Gnomad4 AFR AF: 0.0479

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.0832

Gnomad4 EAS AF: 0.218

Gnomad4 SAS AF: 0.0520

Gnomad4 FIN AF: 0.0257

Gnomad4 NFE AF: 0.0416

Gnomad4 OTH AF: 0.0512

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

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: rs35568106; hg19: chr15-23019694;