rs17137380

Variant names:

• chr15-22852092-A-G
• rs17137380
• NM_030922.7:c.139+222A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030922.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	NM_030922.7	MANE Select	c.139+222A>G		intron	N/A	NP_112184.4
	NIPA2	NM_001008860.3		c.139+222A>G		intron	N/A	NP_001008860.1
	NIPA2	NM_001008892.3		c.139+222A>G		intron	N/A	NP_001008892.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	ENST00000337451.8	TSL:5 MANE Select	c.139+222A>G		intron	N/A	ENSP00000337618.3
	NIPA2	ENST00000398013.7	TSL:1	c.139+222A>G		intron	N/A	ENSP00000381095.3
	NIPA2	ENST00000359727.8	TSL:1	c.139+222A>G		intron	N/A	ENSP00000352762.4

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

African (AFR) AF: 0.00820 AC: 341 AN: 41580

American (AMR) AF: 0.0267 AC: 408 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0565 AC: 196 AN: 3470

East Asian (EAS) AF: 0.234 AC: 1212 AN: 5186

South Asian (SAS) AF: 0.0405 AC: 196 AN: 4834

European-Finnish (FIN) AF: 0.0190 AC: 202 AN: 10620

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0213 AC: 1452 AN: 68040

Other (OTH) AF: 0.0289 AC: 61 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.4
DANN	Benign	0.73
PhyloP100		-0.16

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

Other links and lift over

dbSNP: rs17137380; hg19: chr15-23020976;