Genetic Variant NIPA2:c.196+117_196+123delTTTTTTT (chr15-22853374-CTTTTTTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030922.7(NIPA2):c.196+117_196+123delTTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000823 in 242,930 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000082 ( 0 hom. )

Consequence

NIPA2
NM_030922.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.79

Publications

0 publications found

Variant links:

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]

NIPA2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7 link	c.196+117_196+123delTTTTTTT		intron_variant	Intron 5 of 7	ENST00000337451.8	NP_112184.4	Q8N8Q9-1A0A024R372

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8 link	c.196+107_196+113delTTTTTTT		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3		Q8N8Q9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000823

AC:

AN:

242930

Hom.:

AF XY:

0.00000762

AC XY:

AN XY:

131314

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

6040

American (AMR)

AF:

0.000108

AC:

AN:

9276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6552

East Asian (EAS)

AF:

0.00

AC:

AN:

15454

South Asian (SAS)

AF:

0.00

AC:

AN:

22258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14414

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1186

European-Non Finnish (NFE)

AF:

0.00000645

AC:

AN:

155082

Other (OTH)

AF:

0.00

AC:

AN:

12668

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.225

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.8

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over