Genetic Variant POLD1:c.2154+10C>T (chr19-50409676-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_002691.4(POLD1):c.2154+10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000111 in 1,438,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

POLD1
NM_002691.4 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.94

Publications

1 publications found

Variant links:

Genes affected

POLD1 (HGNC:9175): (DNA polymerase delta 1, catalytic subunit) This gene encodes the 125-kDa catalytic subunit of DNA polymerase delta. DNA polymerase delta possesses both polymerase and 3' to 5' exonuclease activity and plays a critical role in DNA replication and repair. Alternatively spliced transcript variants have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 6. [provided by RefSeq, Mar 2012]

POLD1 Gene-Disease associations (from GenCC):

mandibular hypoplasia-deafness-progeroid syndrome
Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Genomics England PanelApp
POLD1-related polyposis and colorectal cancer syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
colorectal cancer, susceptibility to, 10
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
Polymerase proofreading-related adenomatous polyposis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
immunodeficiency 120
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
non-severe combined immunodeficiency due to polymerase delta deficiency
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

POLD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 19-50409676-C-T is Benign according to our data. Variant chr19-50409676-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 537161.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002691.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POLD1	NM_002691.4	MANE Select	c.2154+10C>T	intron	N/A	NP_002682.2	P28340
POLD1	NM_001308632.1		c.2232+10C>T	intron	N/A	NP_001295561.1	M0R2B7
POLD1	NM_001256849.1		c.2154+10C>T	intron	N/A	NP_001243778.1	P28340

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
POLD1	ENST00000440232.7	TSL:1 MANE Select	c.2154+10C>T	intron	N/A	ENSP00000406046.1	P28340
POLD1	ENST00000595904.6	TSL:1	c.2232+10C>T	intron	N/A	ENSP00000472445.1	M0R2B7
POLD1	ENST00000599857.7	TSL:1	c.2154+10C>T	intron	N/A	ENSP00000473052.1	P28340

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000212

AC:

AN:

236398

AF XY:

0.0000155

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000939

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1438414

Hom.:

Cov.:

AF XY:

0.0000112

AC XY:

AN XY:

711948

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32922

American (AMR)

AF:

0.00

AC:

AN:

42890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25280

East Asian (EAS)

AF:

0.00

AC:

AN:

39270

South Asian (SAS)

AF:

0.000118

AC:

AN:

84406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52080

Middle Eastern (MID)

AF:

0.000202

AC:

AN:

4954

European-Non Finnish (NFE)

AF:

0.00000456

AC:

AN:

1097434

Other (OTH)

AF:

0.00

AC:

AN:

59178

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Colorectal cancer, susceptibility to, 10 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.32

(source)

DANN

Benign

0.37

PhyloP100

-1.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over