rs114406802

Variant names:

• chr15-22860680-A-G
• rs114406802
• NM_030922.7:c.339A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Moderate BP6 BP7

The NM_030922.7(NIPA2):​c.339A>G​(p.Lys113Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000085 in 1,599,852 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00049 (1 hom., cov: 33)
  • Exomes 𝑓: 0.000043 (0 hom.)
• Consequence: NIPA2 NM_030922.7 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.34
• Publications: 0 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.46).
• BP6: Variant 15-22860680-A-G is Benign according to our data. Variant chr15-22860680-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3055976.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=2.34 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	NM_030922.7	MANE Select	c.339A>G	p.Lys113Lys	synonymous	Exon 7 of 8	NP_112184.4
	NIPA2	NM_001008860.3		c.339A>G	p.Lys113Lys	synonymous	Exon 6 of 7	NP_001008860.1	Q8N8Q9-1
	NIPA2	NM_001008892.3		c.339A>G	p.Lys113Lys	synonymous	Exon 5 of 6	NP_001008892.1	Q8N8Q9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	ENST00000337451.8	TSL:5 MANE Select	c.339A>G	p.Lys113Lys	synonymous	Exon 7 of 8	ENSP00000337618.3	Q8N8Q9-1
	NIPA2	ENST00000398013.7	TSL:1	c.339A>G	p.Lys113Lys	synonymous	Exon 5 of 6	ENSP00000381095.3	Q8N8Q9-1
	NIPA2	ENST00000359727.8	TSL:1	c.282A>G	p.Lys94Lys	synonymous	Exon 5 of 6	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes AF: 0.000486 AC: 74 AN: 152174 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00169

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

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: 0.000957

GnomAD2 exomes AF: 0.000135 AC: 32 AN: 237230 AF XY: 0.000148

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.0000332

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000428 AC: 62 AN: 1447560 Hom.: 0 Cov.: 28 AF XY: 0.0000389 AC XY: 28 AN XY: 719796

African (AFR) AF: 0.00164 AC: 54 AN: 32946

American (AMR) AF: 0.0000482 AC: 2 AN: 41530

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25900

East Asian (EAS) AF: 0.00 AC: 0 AN: 39022

South Asian (SAS) AF: 0.00 AC: 0 AN: 82580

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53348

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1106564

Other (OTH) AF: 0.000100 AC: 6 AN: 59922

GnomAD4 genome AF: 0.000486 AC: 74 AN: 152292 Hom.: 1 Cov.: 33 AF XY: 0.000551 AC XY: 41 AN XY: 74472

African (AFR) AF: 0.00168 AC: 70 AN: 41566

American (AMR) AF: 0.000131 AC: 2 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68024

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.000376 Hom.: 0

Bravo AF: 0.000661

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	NIPA2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.46
CADD	Benign	7.1
DANN	Benign	0.73
PhyloP100		2.3

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

Other links and lift over

dbSNP: rs114406802; hg19: chr15-23012388;