10-101579749-G-C

Variant names:

• chr10-101579749-G-C
• rs1188997716
• NM_001174084.2:c.1432C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001174084.2(POLL):​c.1432C>G​(p.Arg478Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,564 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: POLL NM_001174084.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.29

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
POLL	NM_001174084.2	c.1432C>G	p.Arg478Gly	missense_variant	Exon 9 of 9	ENST00000370162.8	NP_001167555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLL	ENST00000370162.8	c.1432C>G	p.Arg478Gly	missense_variant	Exon 9 of 9	1	NM_001174084.2	ENSP00000359181.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000399 AC: 1 AN: 250528 Hom.: 0 AF XY: 0.00000738 AC XY: 1 AN XY: 135494

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 SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461564 Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2 AN XY: 727076

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.078	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	30
DANN	Uncertain	0.99
DEOGEN2	Benign	0.054	T;T;.;T;T;.;T;T;T
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.96	D;.;D;.;D;D;D;D;D
M_CAP	Benign	0.034	D
MetaRNN	Uncertain	0.43	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.2	.;M;.;M;.;.;M;.;.
PrimateAI	Benign	0.21	T
PROVEAN	Pathogenic	-4.6	D;D;D;D;D;.;D;D;D
REVEL	Benign	0.22
Sift	Uncertain	0.0060	D;D;T;D;D;.;D;D;D
Sift4G	Uncertain	0.051	T;D;T;D;D;T;D;.;D
Polyphen		0.90	P;P;P;P;.;.;P;.;.
Vest4		0.22
MutPred		0.54		.;Loss of MoRF binding (P = 0.0335);.;Loss of MoRF binding (P = 0.0335);.;.;Loss of MoRF binding (P = 0.0335);.;.;
MVP		0.65
MPC		0.35
ClinPred		0.97	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.78
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1188997716; hg19: chr10-103339506;