4-2072975-TG-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_181808.4(POLN):c.2509del(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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.675

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
POLN	NM_181808.4	c.2509del	p.Gln837SerfsTer8	frameshift_variant	25/26	ENST00000511885.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
POLN	ENST00000511885.6	c.2509del	p.Gln837SerfsTer8	frameshift_variant	25/26	5	NM_181808.4	P1

Frequencies

GnomAD3 genomes AF: 0.00441 AC: 671 AN: 152174 Hom.: 5 Cov.: 33

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

GnomAD3 exomes AF: 0.00713 AC: 1791 AN: 251032 Hom.: 34 AF XY: 0.00664 AC XY: 902 AN XY: 135742

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 SAS exome AF: 0.00114

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.: 31 AF XY: 0.00581 AC XY: 4221 AN XY: 726872

Gnomad4 AFR exome AF: 0.000568

Gnomad4 AMR exome AF: 0.0105

Gnomad4 ASJ exome AF: 0.00341

Gnomad4 EAS exome AF: 0.0956

Gnomad4 SAS exome AF: 0.00118

Gnomad4 FIN exome AF: 0.00195

Gnomad4 NFE exome AF: 0.00337

Gnomad4 OTH exome AF: 0.00634

GnomAD4 genome AF: 0.00439 AC: 668 AN: 152292 Hom.: 4 Cov.: 33 AF XY: 0.00447 AC XY: 333 AN XY: 74474

Gnomad4 AFR AF: 0.000601

Gnomad4 AMR AF: 0.00575

Gnomad4 ASJ AF: 0.00490

Gnomad4 EAS AF: 0.0549

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.000941

Gnomad4 NFE AF: 0.00326

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00353 Hom.: 2

Bravo AF: 0.00512

Asia WGS AF: 0.0230 AC: 78 AN: 3478

EpiCase AF: 0.00316

EpiControl AF: 0.00314

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Apr 25, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 18, 2019	This variant is associated with the following publications: (PMID: 29074453) -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs3833632; hg19: chr4-2074702;