Genetic Variant NIPA2:c.196+118_196+123delTTTTTT (chr15-22853374-CTTTTTT-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+118_196+123delTTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0000247 in 242,898 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: 𝑓 0.0 ( 0 hom., cov: 23)

Exomes 𝑓: 0.000025 ( 0 hom. )

Failed GnomAD Quality Control

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;

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIPA2	NM_030922.7	MANE Select	c.196+118_196+123delTTTTTT	intron	N/A	NP_112184.4
NIPA2	NM_001008860.3		c.196+118_196+123delTTTTTT	intron	N/A	NP_001008860.1	Q8N8Q9-1
NIPA2	NM_001008892.3		c.196+118_196+123delTTTTTT	intron	N/A	NP_001008892.1	Q8N8Q9-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NIPA2	ENST00000337451.8	TSL:5 MANE Select	c.196+107_196+112delTTTTTT	intron	N/A	ENSP00000337618.3	Q8N8Q9-1
NIPA2	ENST00000398013.7	TSL:1	c.196+107_196+112delTTTTTT	intron	N/A	ENSP00000381095.3	Q8N8Q9-1
NIPA2	ENST00000359727.8	TSL:1	c.139+1505_139+1510delTTTTTT	intron	N/A	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

137240

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

242898

Hom.:

AF XY:

0.0000381

AC XY:

AN XY:

131294

show subpopulations

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

African (AFR)

AF:

0.000331

AC:

AN:

6040

American (AMR)

AF:

0.000216

AC:

AN:

9274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6550

East Asian (EAS)

AF:

0.0000647

AC:

AN:

15454

South Asian (SAS)

AF:

0.0000449

AC:

AN:

22258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

14410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1186

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

155060

Other (OTH)

AF:

0.00

AC:

AN:

12666

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.258

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

137240

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

65964

African (AFR)

AF:

0.00

AC:

AN:

37140

American (AMR)

AF:

0.00

AC:

AN:

13432

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3284

East Asian (EAS)

AF:

0.00

AC:

AN:

4702

South Asian (SAS)

AF:

0.00

AC:

AN:

4368

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7724

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

63558

Other (OTH)

AF:

0.00

AC:

AN:

1866

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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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15-22853374-CTTTTTTT-CT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over