1-92346639-A-G

Variant summary

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

The NM_024813.3(RPAP2):c.1688+725A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 152,084 control chromosomes in the GnomAD database, including 8,341 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 0.30 (8341 hom., cov: 32)
• Consequence: RPAP2 NM_024813.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.187

Genes affected

RPAP2 (HGNC:25791): (RNA polymerase II associated protein 2) Enables RNA polymerase II CTD heptapeptide repeat phosphatase activity. Involved in dephosphorylation of RNA polymerase II C-terminal domain and snRNA transcription. Located in cytosol and nucleolus. Part of RNA polymerase II, holoenzyme. [provided by Alliance of Genome Resources, Apr 2022]

GLMN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPAP2	NM_024813.3	c.1688+725A>G		intron_variant		ENST00000610020.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPAP2	ENST00000610020.2	c.1688+725A>G		intron_variant		1	NM_024813.3	P1
RPAP2	ENST00000477322.1	n.382+725A>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45036 AN: 151966 Hom.: 8335 Cov.: 32

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.260

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.323

Gnomad OTH AF: 0.300

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

GnomAD4 genome AF: 0.296 AC: 45042 AN: 152084 Hom.: 8341 Cov.: 32 AF XY: 0.300 AC XY: 22293 AN XY: 74344

Gnomad4 AFR AF: 0.131

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.345

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.260

Gnomad4 NFE AF: 0.323

Gnomad4 OTH AF: 0.308

Alfa AF: 0.306 Hom.: 1704

Bravo AF: 0.296

Asia WGS AF: 0.580 AC: 2014 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	3.4
Dann	Benign	0.71

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: rs12125484; hg19: chr1-92812196; COSMIC: COSV72101451;