15-22853374-CTTTTTTT-CTTTT

Variant names:

• chr15-22853374-CTTT-C
• rs35568106
• NM_030922.7:c.196+121_196+123delTTT

Variant summary

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

The NM_030922.7(NIPA2):​c.196+121_196+123delTTT variant causes a intron change. The variant allele was found at a frequency of 0.0183 in 376,810 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 0.00017 (0 hom., cov: 23)
  • Exomes 𝑓: 0.029 (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: Variant has high frequency in the AMR (0.0569) population. However there is too low homozygotes in high coverage region: (expected more than 31, got 0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NIPA2	NM_030922.7	c.196+121_196+123delTTT		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+107_196+109delTTT		intron_variant	Intron 5 of 7	5	NM_030922.7	ENSP00000337618.3

Frequencies

GnomAD3 genomes AF: 0.000168 AC: 23 AN: 137202 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000372

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000229

Gnomad FIN AF: 0.000778

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000110

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0287 AC: 6881 AN: 239608 Hom.: 0 AF XY: 0.0288 AC XY: 3733 AN XY: 129518

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

African (AFR) AF: 0.0377 AC: 225 AN: 5968

American (AMR) AF: 0.0611 AC: 557 AN: 9114

Ashkenazi Jewish (ASJ) AF: 0.0268 AC: 173 AN: 6460

East Asian (EAS) AF: 0.0166 AC: 253 AN: 15276

South Asian (SAS) AF: 0.0362 AC: 791 AN: 21880

European-Finnish (FIN) AF: 0.0263 AC: 375 AN: 14254

Middle Eastern (MID) AF: 0.0331 AC: 39 AN: 1178

European-Non Finnish (NFE) AF: 0.0269 AC: 4108 AN: 152978

Other (OTH) AF: 0.0288 AC: 360 AN: 12500

⚠️ 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: 0.000168 AC: 23 AN: 137202 Hom.: 0 Cov.: 23 AF XY: 0.000227 AC XY: 15 AN XY: 65946

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

African (AFR) AF: 0.000108 AC: 4 AN: 37136

American (AMR) AF: 0.000372 AC: 5 AN: 13430

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3282

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

South Asian (SAS) AF: 0.000229 AC: 1 AN: 4368

European-Finnish (FIN) AF: 0.000778 AC: 6 AN: 7710

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

European-Non Finnish (NFE) AF: 0.000110 AC: 7 AN: 63544

Other (OTH) AF: 0.00 AC: 0 AN: 1864

⚠️ 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

ClinVar

Not reported in ClinVar

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

Other links and lift over

dbSNP: rs35568106; hg19: chr15-23019694;