rs9886448

Positions:

• chr8-26512191-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_007257.6(PNMA2):​c.-619+1625A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,210 control chromosomes in the GnomAD database, including 1,968 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.16 (1968 hom., cov: 33)
• Consequence: PNMA2 NM_007257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

Genes affected

PNMA2 (HGNC:9159): (PNMA family member 2) Predicted to be involved in positive regulation of apoptotic process. Predicted to be located in nucleolus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNMA2	NM_007257.6	c.-619+1625A>G		intron_variant		ENST00000522362.7	NP_009188.1
PNMA2	XM_011544365.4	c.-619+637A>G		intron_variant			XP_011542667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNMA2	ENST00000522362.7	c.-619+1625A>G		intron_variant		1	NM_007257.6	ENSP00000429344	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23721 AN: 152092 Hom.: 1951 Cov.: 33

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.193

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.169

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.140

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.156 AC: 23773 AN: 152210 Hom.: 1968 Cov.: 33 AF XY: 0.161 AC XY: 11973 AN XY: 74406

Gnomad4 AFR AF: 0.193

Gnomad4 AMR AF: 0.194

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.219

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.169

Gnomad4 NFE AF: 0.117

Gnomad4 OTH AF: 0.141

Alfa AF: 0.129 Hom.: 1584

Bravo AF: 0.160

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.2
DANN	Benign	0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9886448; hg19: chr8-26369707;