rs5745022

Variant names:

• chr12-132632393-T-A
• rs5745022
• NM_006231.4:c.6252A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-132632393-T-A
• chr12-132632393-T-C
• chr12-132632393-T-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006231.4(POLE):​c.6252A>T​(p.Ser2084Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. S2084S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: POLE NM_006231.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.33

Genes affected

POLE (HGNC:9177): (DNA polymerase epsilon, catalytic subunit) This gene encodes the catalytic subunit of DNA polymerase epsilon. The enzyme is involved in DNA repair and chromosomal DNA replication. Mutations in this gene have been associated with colorectal cancer 12 and facial dysmorphism, immunodeficiency, livedo, and short stature. [provided by RefSeq, Sep 2013]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP7: Synonymous conserved (PhyloP=-4.33 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLE	NM_006231.4	c.6252A>T	p.Ser2084Ser	synonymous_variant	Exon 45 of 49	ENST00000320574.10	NP_006222.2
POLE	XM_011534795.4	c.6252A>T	p.Ser2084Ser	synonymous_variant	Exon 45 of 48		XP_011533097.1
POLE	XM_011534797.4	c.5331A>T	p.Ser1777Ser	synonymous_variant	Exon 37 of 40		XP_011533099.1
POLE	XM_011534802.4	c.3240A>T	p.Ser1080Ser	synonymous_variant	Exon 21 of 24		XP_011533104.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLE	ENST00000320574.10	c.6252A>T	p.Ser2084Ser	synonymous_variant	Exon 45 of 49	1	NM_006231.4	ENSP00000322570.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 41

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.12
DANN	Benign	0.48

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: rs5745022; hg19: chr12-133208979;