rs17137380

Positions:

• chr15-22852092-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030922.7(NIPA2):​c.139+222A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0268 in 152,352 control chromosomes in the GnomAD database, including 202 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.027 (202 hom., cov: 33)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.159

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.223 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.139+222A>G		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.139+222A>G		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 4097 AN: 152234 Hom.: 203 Cov.: 33

Gnomad AFR AF: 0.00823

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0565

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.0413

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.0272

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

GnomAD4 genome AF: 0.0268 AC: 4088 AN: 152352 Hom.: 202 Cov.: 33 AF XY: 0.0285 AC XY: 2127 AN XY: 74514

Gnomad4 AFR AF: 0.00820

Gnomad4 AMR AF: 0.0267

Gnomad4 ASJ AF: 0.0565

Gnomad4 EAS AF: 0.234

Gnomad4 SAS AF: 0.0405

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0213

Gnomad4 OTH AF: 0.0289

Alfa AF: 0.0176 Hom.: 4

Bravo AF: 0.0277

Asia WGS AF: 0.128 AC: 445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.73

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: rs17137380; hg19: chr15-23020976;