15-22853374-CTT-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+122_196+123del variant causes a intron change. The variant allele was found at a frequency of 0.152 in 373,554 control chromosomes in the GnomAD database, including 1,478 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1250 hom., cov: 23)
  • Exomes 𝑓: 0.15 (228 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-CTT-C is Benign according to our data. Variant chr15-22853374-CTT-C is described in ClinVar as [Benign]. Clinvar id is 1260282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.243 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.196+122_196+123del		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.196+122_196+123del		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.153 AC: 20913 AN: 136808 Hom.: 1242 Cov.: 23

Gnomad AFR AF: 0.183

Gnomad AMI AF: 0.106

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.0183

Gnomad SAS AF: 0.136

Gnomad FIN AF: 0.117

Gnomad MID AF: 0.145

Gnomad NFE AF: 0.132

Gnomad OTH AF: 0.162

GnomAD4 exome AF: 0.151 AC: 35818 AN: 236718 Hom.: 228 AF XY: 0.151 AC XY: 19346 AN XY: 127868

Gnomad4 AFR exome AF: 0.187

Gnomad4 AMR exome AF: 0.251

Gnomad4 ASJ exome AF: 0.160

Gnomad4 EAS exome AF: 0.0795

Gnomad4 SAS exome AF: 0.169

Gnomad4 FIN exome AF: 0.149

Gnomad4 NFE exome AF: 0.148

Gnomad4 OTH exome AF: 0.153

GnomAD4 genome AF: 0.153 AC: 20939 AN: 136836 Hom.: 1250 Cov.: 23 AF XY: 0.152 AC XY: 9982 AN XY: 65774

Gnomad4 AFR AF: 0.183

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.0184

Gnomad4 SAS AF: 0.136

Gnomad4 FIN AF: 0.117

Gnomad4 NFE AF: 0.132

Gnomad4 OTH AF: 0.160

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

May 13, 2021

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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;