chr15-22851553-G-A

Position:

• chr15-22851553-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030922.7(NIPA2):​c.-93-86G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 390,054 control chromosomes in the GnomAD database, including 7,708 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3491 hom., cov: 32)
  • Exomes 𝑓: 0.18 (4217 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.992

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-22851553-G-A is Benign according to our data. Variant chr15-22851553-G-A is described in ClinVar as [Benign]. Clinvar id is 1291755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NIPA2	NM_030922.7	c.-93-86G>A		intron_variant		ENST00000337451.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NIPA2	ENST00000337451.8	c.-93-86G>A		intron_variant		5	NM_030922.7	P1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31338 AN: 151750 Hom.: 3483 Cov.: 32

Gnomad AFR AF: 0.230

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.252

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.159

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.180 AC: 42934 AN: 238186 Hom.: 4217 AF XY: 0.179 AC XY: 21883 AN XY: 122352

Gnomad4 AFR exome AF: 0.219

Gnomad4 AMR exome AF: 0.322

Gnomad4 ASJ exome AF: 0.219

Gnomad4 EAS exome AF: 0.200

Gnomad4 SAS exome AF: 0.162

Gnomad4 FIN exome AF: 0.157

Gnomad4 NFE exome AF: 0.168

Gnomad4 OTH exome AF: 0.196

GnomAD4 genome AF: 0.207 AC: 31376 AN: 151868 Hom.: 3491 Cov.: 32 AF XY: 0.208 AC XY: 15471 AN XY: 74234

Gnomad4 AFR AF: 0.230

Gnomad4 AMR AF: 0.310

Gnomad4 ASJ AF: 0.225

Gnomad4 EAS AF: 0.252

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.159

Gnomad4 NFE AF: 0.174

Gnomad4 OTH AF: 0.217

Alfa AF: 0.194 Hom.: 437

Bravo AF: 0.217

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.6
DANN	Benign	0.12

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: rs7171241; hg19: chr15-23021515;