6-57257165-T-G

Position:

• chr6-57257165-T-G

Variant summary

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

The XM_047418987.1(PRIM2):​c.-10+35448T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 152,104 control chromosomes in the GnomAD database, including 5,977 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 0.24 (5977 hom., cov: 33)
• Consequence: PRIM2 XM_047418987.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.564

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRIM2	XM_047418987.1	c.-10+35448T>G		intron_variant			XP_047274943.1
		n.57257165T>G		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35770 AN: 151986 Hom.: 5961 Cov.: 33

Gnomad AFR AF: 0.474

Gnomad AMI AF: 0.152

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.128

Gnomad EAS AF: 0.0321

Gnomad SAS AF: 0.0915

Gnomad FIN AF: 0.118

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.236 AC: 35828 AN: 152104 Hom.: 5977 Cov.: 33 AF XY: 0.227 AC XY: 16914 AN XY: 74386

Gnomad4 AFR AF: 0.474

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.128

Gnomad4 EAS AF: 0.0322

Gnomad4 SAS AF: 0.0920

Gnomad4 FIN AF: 0.118

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.194

Alfa AF: 0.236 Hom.: 821

Bravo AF: 0.246

Asia WGS AF: 0.0820 AC: 284 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.65
DANN	Benign	0.41

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs13213618; hg19: chr6-57121963;