Genetic Variant NIPA2:c.-93-86G>A (chr15-22851553-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.992

Publications

3 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: Benign. The variant received -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 rank	MANE	Protein	UniProt
NIPA2	NM_030922.7 link	c.-93-86G>A		intron_variant	Intron 3 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.-93-86G>A		intron_variant	Intron 3 of 7	5	NM_030922.7	ENSP00000337618.3		Q8N8Q9-1

Frequencies

GnomAD3 genomes

AF:

0.207

AC:

31338

AN:

151750

Hom.:

3483

Cov.:

show subpopulations

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

show subpopulations

African (AFR)

AF:

0.219

AC:

1521

AN:

6954

American (AMR)

AF:

0.322

AC:

2420

AN:

7514

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

1874

AN:

8552

East Asian (EAS)

AF:

0.200

AC:

4121

AN:

20656

South Asian (SAS)

AF:

0.162

AC:

1023

AN:

6302

European-Finnish (FIN)

AF:

0.157

AC:

2969

AN:

18858

Middle Eastern (MID)

AF:

0.244

AC:

286

AN:

1170

European-Non Finnish (NFE)

AF:

0.168

AC:

25714

AN:

152882

Other (OTH)

AF:

0.196

AC:

3006

AN:

15298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

1585

3170

4754

6339

7924

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.207

AC:

31376

AN:

151868

Hom.:

3491

Cov.:

AF XY:

0.208

AC XY:

15471

AN XY:

74234

show subpopulations

African (AFR)

AF:

0.230

AC:

9511

AN:

41402

American (AMR)

AF:

0.310

AC:

4719

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.225

AC:

782

AN:

3470

East Asian (EAS)

AF:

0.252

AC:

1308

AN:

5184

South Asian (SAS)

AF:

0.197

AC:

946

AN:

4812

European-Finnish (FIN)

AF:

0.159

AC:

1665

AN:

10504

Middle Eastern (MID)

AF:

0.253

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.174

AC:

11809

AN:

67948

Other (OTH)

AF:

0.217

AC:

458

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1250

2500

3750

5000

6250

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.195

Hom.:

455

Bravo

AF:

0.217

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

May 14, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.6

(source)

DANN

Benign

0.12

PhyloP100

0.99

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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15-22851553-G-A

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