Genetic Variant POLL:c.*68C>T (chr10-101579385-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174084.2(POLL):c.*68C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 1,513,876 control chromosomes in the GnomAD database, including 4,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.076 ( 479 hom., cov: 32)

Exomes 𝑓: 0.072 ( 3825 hom. )

Consequence

POLL
NM_001174084.2 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.163

Variant links:

Genes affected

POLL (HGNC:9184): (DNA polymerase lambda) This gene encodes a DNA polymerase. DNA polymerases catalyze DNA-template-directed extension of the 3'-end of a DNA strand. This particular polymerase, which is a member of the X family of DNA polymerases, likely plays a role in non-homologous end joining and other DNA repair processes. Alternatively spliced transcript variants have been described. [provided by RefSeq, Mar 2010]

POLL links:

DPCD (HGNC:24542): (deleted in primary ciliary dyskinesia homolog (mouse)) This gene in mouse encodes a protein that may be involved in the generation and maintenance of ciliated cells. In mouse, expression of this gene increases during ciliated cell differentiation, and disruption of this gene has been linked to primary ciliary dyskinesia. [provided by RefSeq, Jul 2016]

DPCD links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 10-101579385-G-A is Benign according to our data. Variant chr10-101579385-G-A is described in ClinVar as [Benign]. Clinvar id is 1279768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLL	NM_001174084.2 link	c.*68C>T		3_prime_UTR_variant	Exon 9 of 9	ENST00000370162.8	NP_001167555.1	Q9UGP5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLL	ENST00000370162 link	c.*68C>T		3_prime_UTR_variant	Exon 9 of 9	1	NM_001174084.2	ENSP00000359181.3		Q9UGP5-1

Frequencies

GnomAD3 genomes

AF:

0.0762

AC:

11591

AN:

152032

Hom.:

477

Cov.:

show subpopulations

Gnomad AFR

AF:

0.104

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0622

Gnomad ASJ

AF:

0.0502

Gnomad EAS

AF:

0.00194

Gnomad SAS

AF:

0.0400

Gnomad FIN

AF:

0.0580

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0744

Gnomad OTH

AF:

0.0626

GnomAD4 exome

AF:

0.0723

AC:

98454

AN:

1361726

Hom.:

3825

Cov.:

AF XY:

0.0715

AC XY:

47927

AN XY:

670750

show subpopulations

Gnomad4 AFR exome

AF:

0.105

Gnomad4 AMR exome

AF:

0.0484

Gnomad4 ASJ exome

AF:

0.0506

Gnomad4 EAS exome

AF:

0.000820

Gnomad4 SAS exome

AF:

0.0423

Gnomad4 FIN exome

AF:

0.0643

Gnomad4 NFE exome

AF:

0.0780

Gnomad4 OTH exome

AF:

0.0656

GnomAD4 genome

AF:

0.0763

AC:

11608

AN:

152150

Hom.:

479

Cov.:

AF XY:

0.0741

AC XY:

5509

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.104

Gnomad4 AMR

AF:

0.0623

Gnomad4 ASJ

AF:

0.0502

Gnomad4 EAS

AF:

0.00194

Gnomad4 SAS

AF:

0.0399

Gnomad4 FIN

AF:

0.0580

Gnomad4 NFE

AF:

0.0743

Gnomad4 OTH

AF:

0.0676

Alfa

AF:

0.0704

Hom.:

423

Bravo

AF:

0.0769

Asia WGS

AF:

0.0470

AC:

164

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.4

DANN

Benign

0.75

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over