chr6-57341122-G-A

Position:

• chr6-57341122-G-A

Variant summary

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

The NM_000947.5(PRIM2):​c.459+15077G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.598 in 151,952 control chromosomes in the GnomAD database, including 27,278 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 0.60 (27278 hom., cov: 31)
• Consequence: PRIM2 NM_000947.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.336

Genes affected

PRIM2 (HGNC:9370): (DNA primase subunit 2) This gene encodes the 58 kilodalton subunit of DNA primase, an enzyme that plays a key role in the replication of DNA. The encoded protein forms a heterodimer with a 49 kilodalton subunit. This heterodimer functions as a DNA-directed RNA polymerase to synthesize small RNA primers that are used to create Okazaki fragments on the lagging strand of the DNA. Alternative splicing of this gene results in multiple transcript variants. This gene has a related pseudogene, which is also present on chromosome 6. [provided by RefSeq, Apr 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRIM2	NM_000947.5	c.459+15077G>A		intron_variant		ENST00000615550.5	NP_000938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PRIM2	ENST00000615550.5	c.459+15077G>A		intron_variant		1	NM_000947.5	ENSP00000484105	P1
PRIM2	ENST00000671770.1	c.459+15077G>A		intron_variant				ENSP00000500602
PRIM2	ENST00000672107.1	c.459+15077G>A		intron_variant				ENSP00000500708
PRIM2	ENST00000419977.4	n.542+15077G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.598 AC: 90826 AN: 151834 Hom.: 27247 Cov.: 31

Gnomad AFR AF: 0.629

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.537

Gnomad ASJ AF: 0.609

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.703

Gnomad FIN AF: 0.602

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.593

Gnomad OTH AF: 0.587

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

GnomAD4 genome AF: 0.598 AC: 90901 AN: 151952 Hom.: 27278 Cov.: 31 AF XY: 0.596 AC XY: 44291 AN XY: 74258

Gnomad4 AFR AF: 0.629

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.609

Gnomad4 EAS AF: 0.491

Gnomad4 SAS AF: 0.704

Gnomad4 FIN AF: 0.602

Gnomad4 NFE AF: 0.593

Gnomad4 OTH AF: 0.582

Alfa AF: 0.589 Hom.: 30385

Bravo AF: 0.587

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.53
DANN	Benign	0.54

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: rs6459193; hg19: chr6-57205920;