15-22853374-C-CTTTT

Variant names:

• chr15-22853374-C-CTTTT
• rs35568106
• NM_030922.7:c.196+120_196+123dupTTTT

Variant summary

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

The NM_030922.7(NIPA2):​c.196+120_196+123dupTTTT variant causes a intron change. The variant allele was found at a frequency of 0.0000263 in 380,164 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: 𝑓 0.0000073 (0 hom., cov: 23)
  • Exomes 𝑓: 0.000037 (0 hom.)
• Consequence: NIPA2 NM_030922.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.79
• Publications: 1 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.196+120_196+123dupTTTT		intron_variant	Intron 5 of 7	ENST00000337451.8	NP_112184.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NIPA2	ENST00000337451.8	c.196+106_196+107insTTTT		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.00000729 AC: 1 AN: 137242 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000157

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000370 AC: 9 AN: 242922 Hom.: 0 AF XY: 0.0000228 AC XY: 3 AN XY: 131310

⚠️ 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: 0.000135 AC: 3 AN: 22256

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: 0.0000387 AC: 6 AN: 155076

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

⚠️ 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.

GnomAD4 genome AF: 0.00000729 AC: 1 AN: 137242 Hom.: 0 Cov.: 23 AF XY: 0.0000152 AC XY: 1 AN XY: 65964

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

African (AFR) AF: 0.00 AC: 0 AN: 37142

American (AMR) AF: 0.00 AC: 0 AN: 13432

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3284

East Asian (EAS) AF: 0.00 AC: 0 AN: 4702

South Asian (SAS) AF: 0.00 AC: 0 AN: 4368

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7724

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000157 AC: 1 AN: 63558

Other (OTH) AF: 0.00 AC: 0 AN: 1866

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;