chr15-22853374-C-CTTTTT

Variant names:

• chr15-22853374-C-CTTTTT
• rs35568106
• NM_030922.7:c.196+119_196+123dupTTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_030922.7(NIPA2):​c.196+119_196+123dupTTTTT variant causes a intron change. The variant allele was found at a frequency of 0.00000412 in 242,926 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: not found (cov: 23)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79
• 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: 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NIPA2	NM_030922.7	MANE Select	c.196+119_196+123dupTTTTT		intron	N/A	NP_112184.4
	NIPA2	NM_001008860.3		c.196+119_196+123dupTTTTT		intron	N/A	NP_001008860.1	Q8N8Q9-1
	NIPA2	NM_001008892.3		c.196+119_196+123dupTTTTT		intron	N/A	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.196+106_196+107insTTTTT		intron	N/A	ENSP00000337618.3	Q8N8Q9-1
	NIPA2	ENST00000398013.7	TSL:1	c.196+106_196+107insTTTTT		intron	N/A	ENSP00000381095.3	Q8N8Q9-1
	NIPA2	ENST00000359727.8	TSL:1	c.139+1504_139+1505insTTTTT		intron	N/A	ENSP00000352762.4	Q8N8Q9-2

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 0.00000412 AC: 1 AN: 242926 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131312

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

African (AFR) AF: 0.00 AC: 0 AN: 6040

American (AMR) AF: 0.00 AC: 0 AN: 9276

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6552

East Asian (EAS) AF: 0.00 AC: 0 AN: 15454

South Asian (SAS) AF: 0.00 AC: 0 AN: 22258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1186

European-Non Finnish (NFE) AF: 0.00000645 AC: 1 AN: 155078

Other (OTH) AF: 0.00 AC: 0 AN: 12668

⚠️ 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.

GnomAD4 genome Cov.: 23

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

Other links and lift over

dbSNP: rs35568106; hg19: chr15-23019694;