15-22839265-A-G

Position:

• chr15-22839265-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.-352+344A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.887 in 152,276 control chromosomes in the GnomAD database, including 60,093 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 0.89 (60088 hom., cov: 33)
  • Exomes 𝑓: 1.0 (5 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.637

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.959 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.-352+344A>G		intron_variant		ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.-352+344A>G		intron_variant		5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.886 AC: 134864 AN: 152148 Hom.: 60028 Cov.: 33

Gnomad AFR AF: 0.966

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.888

Gnomad ASJ AF: 0.844

Gnomad EAS AF: 0.930

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.877

Gnomad NFE AF: 0.832

Gnomad OTH AF: 0.879

GnomAD4 exome AF: 1.00 AC: 10 AN: 10 Hom.: 5 AF XY: 1.00 AC XY: 8 AN XY: 8

Gnomad4 AFR exome AF: 1.00

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 1.00

GnomAD4 genome AF: 0.887 AC: 134985 AN: 152266 Hom.: 60088 Cov.: 33 AF XY: 0.891 AC XY: 66336 AN XY: 74454

Gnomad4 AFR AF: 0.966

Gnomad4 AMR AF: 0.888

Gnomad4 ASJ AF: 0.844

Gnomad4 EAS AF: 0.930

Gnomad4 SAS AF: 0.911

Gnomad4 FIN AF: 0.908

Gnomad4 NFE AF: 0.832

Gnomad4 OTH AF: 0.879

Alfa AF: 0.843 Hom.: 114510

Bravo AF: 0.889

Asia WGS AF: 0.911 AC: 3166 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.5
DANN	Benign	0.53

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: rs4592619; hg19: chr15-23033803;