rs4872449

Positions:

• chr8-26512998-G-A

Variant summary

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

The NM_007257.6(PNMA2):​c.-619+818C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,152 control chromosomes in the GnomAD database, including 10,985 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 0.34 (10980 hom., cov: 32)
  • Exomes 𝑓: 0.46 (5 hom.)
• Consequence: PNMA2 NM_007257.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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]

PNMA2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PNMA2	NM_007257.6	c.-619+818C>T		intron_variant		ENST00000522362.7	NP_009188.1
PNMA2	XM_011544365.4	c.-789C>T		5_prime_UTR_premature_start_codon_gain_variant	1/3		XP_011542667.1
PNMA2	XM_011544365.4	c.-789C>T		5_prime_UTR_variant	1/3		XP_011542667.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PNMA2	ENST00000522362.7	c.-619+818C>T		intron_variant		1	NM_007257.6	ENSP00000429344.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51861 AN: 151978 Hom.: 10981 Cov.: 32

Gnomad AFR AF: 0.0930

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.419

Gnomad EAS AF: 0.670

Gnomad SAS AF: 0.193

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.433

Gnomad OTH AF: 0.373

GnomAD4 exome AF: 0.464 AC: 26 AN: 56 Hom.: 5 Cov.: 0 AF XY: 0.500 AC XY: 18 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.474

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.341 AC: 51853 AN: 152096 Hom.: 10980 Cov.: 32 AF XY: 0.342 AC XY: 25459 AN XY: 74338

Gnomad4 AFR AF: 0.0928

Gnomad4 AMR AF: 0.443

Gnomad4 ASJ AF: 0.419

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.194

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.433

Gnomad4 OTH AF: 0.370

Alfa AF: 0.424 Hom.: 22512

Bravo AF: 0.340

Asia WGS AF: 0.410 AC: 1424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	11
DANN	Benign	0.90

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

Publications

LitVar

Other links and lift over

dbSNP: rs4872449; hg19: chr8-26370514;