Genetic Variant NIPA2:c.196+123delT (chr15-22853374-CT-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_030922.7(NIPA2):c.196+123delT variant causes a intron change. The variant allele was found at a frequency of 0.154 in 377,258 control chromosomes in the GnomAD database, including 197 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.050 ( 171 hom., cov: 23)

Exomes 𝑓: 0.21 ( 26 hom. )

Consequence

NIPA2
NM_030922.7 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

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: Benign. The variant received -10 ACMG points.

BP6

Variant 15-22853374-CT-C is Benign according to our data. Variant chr15-22853374-CT-C is described in ClinVar as [Benign]. Clinvar id is 1245041.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7 link	c.196+123delT		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+107delT		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3		Q8N8Q9-1

Frequencies

GnomAD3 genomes

AF:

0.0499

AC:

6848

AN:

137100

Hom.:

172

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0478

Gnomad AMI

AF:

0.00114

Gnomad AMR

AF:

0.0440

Gnomad ASJ

AF:

0.0832

Gnomad EAS

AF:

0.217

Gnomad SAS

AF:

0.0525

Gnomad FIN

AF:

0.0257

Gnomad MID

AF:

0.0925

Gnomad NFE

AF:

0.0416

Gnomad OTH

AF:

0.0489

GnomAD4 exome

AF:

0.214

AC:

51391

AN:

240134

Hom.:

AF XY:

0.214

AC XY:

27784

AN XY:

129764

show subpopulations

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

African (AFR)

AF:

0.209

AC:

1251

AN:

5980

American (AMR)

AF:

0.182

AC:

1670

AN:

9180

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

1411

AN:

6490

East Asian (EAS)

AF:

0.297

AC:

4536

AN:

15280

South Asian (SAS)

AF:

0.216

AC:

4753

AN:

21954

European-Finnish (FIN)

AF:

0.200

AC:

2841

AN:

14238

Middle Eastern (MID)

AF:

0.199

AC:

234

AN:

1176

European-Non Finnish (NFE)

AF:

0.209

AC:

32005

AN:

153308

Other (OTH)

AF:

0.215

AC:

2690

AN:

12528

⚠️ 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: 0.368

Heterozygous variant carriers

3066

6133

9199

12266

15332

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0500

AC:

6850

AN:

137124

Hom.:

171

Cov.:

AF XY:

0.0512

AC XY:

3374

AN XY:

65946

show subpopulations

African (AFR)

AF:

0.0479

AC:

1783

AN:

37186

American (AMR)

AF:

0.0440

AC:

591

AN:

13440

Ashkenazi Jewish (ASJ)

AF:

0.0832

AC:

273

AN:

3282

East Asian (EAS)

AF:

0.218

AC:

1018

AN:

4676

South Asian (SAS)

AF:

0.0520

AC:

226

AN:

4344

European-Finnish (FIN)

AF:

0.0257

AC:

198

AN:

7708

Middle Eastern (MID)

AF:

0.0858

AC:

AN:

268

European-Non Finnish (NFE)

AF:

0.0416

AC:

2641

AN:

63472

Other (OTH)

AF:

0.0512

AC:

AN:

1874

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

Heterozygous variant carriers

261

522

784

1045

1306

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Aug 20, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

3.8

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

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15-22853374-CT-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over