10-101579385-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.163

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]

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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/exons	MANE	UniProt
POLL	NM_001174084.2	c.*68C>T		3_prime_UTR_variant	9/9	ENST00000370162.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLL	ENST00000370162.8	c.*68C>T		3_prime_UTR_variant	9/9	1	NM_001174084.2	P1

Frequencies

GnomAD3 genomes AF: 0.0762 AC: 11591 AN: 152032 Hom.: 477 Cov.: 32

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.: 29 AF XY: 0.0715 AC XY: 47927 AN XY: 670750

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.: 32 AF XY: 0.0741 AC XY: 5509 AN XY: 74386

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 15, 2021

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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

Other links and lift over

dbSNP: rs3730478; hg19: chr10-103339142; COSMIC: COSV54574132; COSMIC: COSV54574132;