14-49647358-G-A

Variant names:

• chr14-49647358-G-A
• rs1166301753
• NM_002692.4:c.1500C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_002692.4(POLE2):​c.1500C>T​(p.Gly500Gly) variant causes a splice region, 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. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: POLE2 NM_002692.4 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.574
• Publications: 0 publications found

Genes affected

POLE2 (HGNC:9178): (DNA polymerase epsilon 2, accessory subunit) DNA polymerase epsilon, which is involved in DNA repair and replication, is composed of a large catalytic subunit and a small accessory subunit. The protein encoded by this gene represents the small subunit (B). Defects in this gene have been linked to colorectal cancer and to combined immunodeficiency. [provided by RefSeq, Jan 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 14-49647358-G-A is Benign according to our data. Variant chr14-49647358-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2037703.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.574 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002692.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLE2	NM_002692.4	MANE Select	c.1500C>T	p.Gly500Gly	splice_region synonymous	Exon 18 of 19	NP_002683.2
	POLE2	NM_001348384.2		c.1497C>T	p.Gly499Gly	splice_region synonymous	Exon 18 of 19	NP_001335313.1
	POLE2	NM_001197330.2		c.1422C>T	p.Gly474Gly	splice_region synonymous	Exon 17 of 18	NP_001184259.1	P56282-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLE2	ENST00000216367.10	TSL:1 MANE Select	c.1500C>T	p.Gly500Gly	splice_region synonymous	Exon 18 of 19	ENSP00000216367.5	P56282-1
	POLE2	ENST00000539565.6	TSL:1	c.1422C>T	p.Gly474Gly	splice_region synonymous	Exon 17 of 18	ENSP00000446313.2	P56282-2
	POLE2	ENST00000960548.1		c.1422C>T	p.Gly474Gly	splice_region synonymous	Exon 17 of 18	ENSP00000630607.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1400998 Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0 AN XY: 697958

African (AFR) AF: 0.00 AC: 0 AN: 31062

American (AMR) AF: 0.00 AC: 0 AN: 38756

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24904

East Asian (EAS) AF: 0.00 AC: 0 AN: 37126

South Asian (SAS) AF: 0.00 AC: 0 AN: 78114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52252

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5344

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1075664

Other (OTH) AF: 0.00 AC: 0 AN: 57776

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000189

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	9.4
DANN	Benign	0.70
PhyloP100		0.57

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

Other links and lift over

dbSNP: rs1166301753; hg19: chr14-50114076;