Genetic Variant NIPA2:c.196+123dupT (chr15-22853374-C-CT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_030922.7(NIPA2):c.196+123dupT variant causes a intron change. The variant allele was found at a frequency of 0.0507 in 379,184 control chromosomes in the GnomAD database, including 11 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0070 ( 11 hom., cov: 23)

Exomes 𝑓: 0.075 ( 0 hom. )

Consequence

NIPA2
NM_030922.7 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.79

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 11 AR gene

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+123dupT	intron	N/A	NP_112184.4
NIPA2	NM_001008860.3		c.196+123dupT	intron	N/A	NP_001008860.1	Q8N8Q9-1
NIPA2	NM_001008892.3		c.196+123dupT	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+106_196+107insT	intron	N/A	ENSP00000337618.3	Q8N8Q9-1
NIPA2	ENST00000398013.7	TSL:1	c.196+106_196+107insT	intron	N/A	ENSP00000381095.3	Q8N8Q9-1
NIPA2	ENST00000359727.8	TSL:1	c.139+1504_139+1505insT	intron	N/A	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes

AF:

0.00699

AC:

959

AN:

137216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0161

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00432

Gnomad ASJ

AF:

0.0122

Gnomad EAS

AF:

0.00404

Gnomad SAS

AF:

0.00710

Gnomad FIN

AF:

0.00272

Gnomad MID

AF:

0.00685

Gnomad NFE

AF:

0.00285

Gnomad OTH

AF:

0.00536

GnomAD4 exome

AF:

0.0754

AC:

18249

AN:

241944

Hom.:

AF XY:

0.0755

AC XY:

9874

AN XY:

130774

show subpopulations

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

African (AFR)

AF:

0.0779

AC:

469

AN:

6020

American (AMR)

AF:

0.0528

AC:

488

AN:

9242

Ashkenazi Jewish (ASJ)

AF:

0.0754

AC:

492

AN:

6528

East Asian (EAS)

AF:

0.0765

AC:

1175

AN:

15358

South Asian (SAS)

AF:

0.0708

AC:

1569

AN:

22170

European-Finnish (FIN)

AF:

0.0731

AC:

1050

AN:

14372

Middle Eastern (MID)

AF:

0.0541

AC:

AN:

1184

European-Non Finnish (NFE)

AF:

0.0779

AC:

12025

AN:

154454

Other (OTH)

AF:

0.0727

AC:

917

AN:

12616

⚠️ 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: 0.334

Heterozygous variant carriers

1448

2896

4345

5793

7241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

130

260

390

520

650

<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

AF:

0.00698

AC:

958

AN:

137240

Hom.:

Cov.:

AF XY:

0.00715

AC XY:

472

AN XY:

65990

show subpopulations

African (AFR)

AF:

0.0160

AC:

596

AN:

37202

American (AMR)

AF:

0.00431

AC:

AN:

13442

Ashkenazi Jewish (ASJ)

AF:

0.0122

AC:

AN:

3284

East Asian (EAS)

AF:

0.00405

AC:

AN:

4686

South Asian (SAS)

AF:

0.00713

AC:

AN:

4350

European-Finnish (FIN)

AF:

0.00272

AC:

AN:

7724

Middle Eastern (MID)

AF:

0.00373

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.00286

AC:

182

AN:

63532

Other (OTH)

AF:

0.00532

AC:

AN:

1878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

125

156

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

15-22853374-CTTTTTTT-CTTTTTTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over