10-101584832-T-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001174084.2(POLL):c.661A>C(p.Thr221Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0727 in 1,536,680 control chromosomes in the GnomAD database, including 4,358 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.077 ( 483 hom., cov: 32)

Exomes 𝑓: 0.072 ( 3875 hom. )

Consequence

POLL
NM_001174084.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.659

Publications

25 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0016044974).

BP6

Variant 10-101584832-T-G is Benign according to our data. Variant chr10-101584832-T-G is described in ClinVar as Benign. ClinVar VariationId is 1241876.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLL	NM_001174084.2 link	c.661A>C	p.Thr221Pro	missense_variant	Exon 5 of 9	ENST00000370162.8	NP_001167555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLL	ENST00000370162.8 link	c.661A>C	p.Thr221Pro	missense_variant	Exon 5 of 9	1	NM_001174084.2	ENSP00000359181.3

Frequencies

GnomAD3 genomes

AF:

0.0766

AC:

11636

AN:

151956

Hom.:

481

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.0624

Gnomad ASJ

AF:

0.0504

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.0405

Gnomad FIN

AF:

0.0582

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0744

Gnomad OTH

AF:

0.0629

GnomAD2 exomes

AF:

0.0619

AC:

12730

AN:

205810

AF XY:

0.0616

show subpopulations

Gnomad AFR exome

AF:

0.103

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.0502

Gnomad EAS exome

AF:

0.00112

Gnomad FIN exome

AF:

0.0593

Gnomad NFE exome

AF:

0.0735

Gnomad OTH exome

AF:

0.0636

GnomAD4 exome

AF:

0.0722

AC:

100036

AN:

1384606

Hom.:

3875

Cov.:

AF XY:

0.0715

AC XY:

48906

AN XY:

683678

show subpopulations

African (AFR)

AF:

0.105

AC:

3292

AN:

31356

American (AMR)

AF:

0.0479

AC:

1724

AN:

35956

Ashkenazi Jewish (ASJ)

AF:

0.0503

AC:

1131

AN:

22494

East Asian (EAS)

AF:

0.000794

AC:

AN:

37772

South Asian (SAS)

AF:

0.0424

AC:

3158

AN:

74562

European-Finnish (FIN)

AF:

0.0634

AC:

3233

AN:

50984

Middle Eastern (MID)

AF:

0.0341

AC:

185

AN:

5422

European-Non Finnish (NFE)

AF:

0.0782

AC:

83602

AN:

1069522

Other (OTH)

AF:

0.0651

AC:

3681

AN:

56538

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

4393

8786

13178

17571

21964

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3186

6372

9558

12744

15930

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0766

AC:

11655

AN:

152074

Hom.:

483

Cov.:

AF XY:

0.0745

AC XY:

5539

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.105

AC:

4353

AN:

41486

American (AMR)

AF:

0.0625

AC:

954

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.0504

AC:

175

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5184

South Asian (SAS)

AF:

0.0403

AC:

194

AN:

4816

European-Finnish (FIN)

AF:

0.0582

AC:

616

AN:

10580

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0744

AC:

5056

AN:

67962

Other (OTH)

AF:

0.0679

AC:

143

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

562

1124

1686

2248

2810

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

128

256

384

512

640

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0697

Hom.:

1141

Bravo

AF:

0.0773

TwinsUK

AF:

0.0766

AC:

284

ALSPAC

AF:

0.0820

AC:

316

ESP6500AA

AF:

0.0983

AC:

433

ESP6500EA

AF:

0.0724

AC:

623

ExAC

AF:

0.0610

AC:

7397

Asia WGS

AF:

0.0470

AC:

166

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 04, 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

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.51

CADD

Benign

8.7

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.056

T;T;T;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.17

.;.;T;T;T;T

MetaRNN

Benign

0.0016

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;L;.;.

PhyloP100

0.66

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.80

N;N;N;N;N;N

REVEL

Benign

0.094

Sift

Benign

0.19

T;T;T;T;T;T

Sift4G

Benign

0.20

T;T;T;T;.;.

Polyphen

0.23

B;B;.;B;.;.

Vest4

0.024

MPC

0.21

ClinPred

0.0024

GERP RS

3.6

Varity_R

0.081

gMVP

0.21

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.13

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over