Genetic Variant POLN:p.Gln837SerfsTer8 (chr4-2072975-TG-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_181808.4(POLN):c.2509delC(p.Gln837SerfsTer8) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00581 in 1,613,342 control chromosomes in the GnomAD database, including 217 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 4 hom., cov: 33)

Exomes 𝑓: 0.0060 ( 213 hom. )

Consequence

POLN
NM_181808.4 frameshift

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 0.675

Variant links:

Genes affected

POLN (HGNC:18870): (DNA polymerase nu) This gene encodes a DNA polymerase type-A family member. The encoded protein plays a role in DNA repair and homologous recombination. This gene shares its 5' exons with some transcripts from overlapping GeneID: 79441, which encodes an augmentin-like protein complex subunit. [provided by RefSeq, Dec 2014]

POLN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 4-2072975-TG-T is Benign according to our data. Variant chr4-2072975-TG-T is described in ClinVar as [Benign]. Clinvar id is 715710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.093 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLN	NM_181808.4 link	c.2509delC	p.Gln837SerfsTer8	frameshift_variant	Exon 25 of 26	ENST00000511885.6	NP_861524.2	Q7Z5Q5-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLN	ENST00000511885.6 link	c.2509delC	p.Gln837SerfsTer8	frameshift_variant	Exon 25 of 26	5	NM_181808.4	ENSP00000435506.1		Q7Z5Q5-1

Frequencies

GnomAD3 genomes

AF:

0.00441

AC:

671

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00576

Gnomad ASJ

AF:

0.00490

Gnomad EAS

AF:

0.0546

Gnomad SAS

AF:

0.00248

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00326

Gnomad OTH

AF:

0.00621

GnomAD2 exomes

AF:

0.00713

AC:

1791

AN:

251032

AF XY:

0.00664

show subpopulations

Gnomad AFR exome

AF:

0.000493

Gnomad AMR exome

AF:

0.0115

Gnomad ASJ exome

AF:

0.00357

Gnomad EAS exome

AF:

0.0513

Gnomad FIN exome

AF:

0.00131

Gnomad NFE exome

AF:

0.00267

Gnomad OTH exome

AF:

0.00669

GnomAD4 exome

AF:

0.00596

AC:

8713

AN:

1461050

Hom.:

213

Cov.:

AF XY:

0.00581

AC XY:

4221

AN XY:

726872

show subpopulations

Gnomad4 AFR exome

AF:

0.000568

AC:

AN:

33478

Gnomad4 AMR exome

AF:

0.0105

AC:

469

AN:

44708

Gnomad4 ASJ exome

AF:

0.00341

AC:

AN:

26126

Gnomad4 EAS exome

AF:

0.0956

AC:

3794

AN:

39694

Gnomad4 SAS exome

AF:

0.00118

AC:

102

AN:

86244

Gnomad4 FIN exome

AF:

0.00195

AC:

103

AN:

52762

Gnomad4 NFE exome

AF:

0.00337

AC:

3749

AN:

1111904

Gnomad4 Remaining exome

AF:

0.00634

AC:

383

AN:

60372

Heterozygous variant carriers

395

790

1184

1579

1974

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

198

396

594

792

990

<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:

0.00439

AC:

668

AN:

152292

Hom.:

Cov.:

AF XY:

0.00447

AC XY:

333

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000601

AC:

0.000601482

AN:

0.000601482

Gnomad4 AMR

AF:

0.00575

AC:

0.00574788

AN:

0.00574788

Gnomad4 ASJ

AF:

0.00490

AC:

0.00489914

AN:

0.00489914

Gnomad4 EAS

AF:

0.0549

AC:

0.0549323

AN:

0.0549323

Gnomad4 SAS

AF:

0.00228

AC:

0.00227743

AN:

0.00227743

Gnomad4 FIN

AF:

0.000941

AC:

0.000941265

AN:

0.000941265

Gnomad4 NFE

AF:

0.00326

AC:

0.00326451

AN:

0.00326451

Gnomad4 OTH

AF:

0.00473

AC:

0.00473037

AN:

0.00473037

Heterozygous variant carriers

110

147

184

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

<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:

0.00353

Hom.:

Bravo

AF:

0.00512

Asia WGS

AF:

0.0230

AC:

AN:

3478

EpiCase

AF:

0.00316

EpiControl

AF:

0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jan 18, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29074453) -

Apr 25, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Mutation Taster

=180/20

polymorphism

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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