7-44122210-A-G

Position:

• chr7-44122210-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001127218.3(POLD2):​c.-157T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 1,436,950 control chromosomes in the GnomAD database, including 47,776 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.24 (4468 hom., cov: 33)
  • Exomes 𝑓: 0.26 (43308 hom.)
• Consequence: POLD2 NM_001127218.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.244

Genes affected

POLD2 (HGNC:9176): (DNA polymerase delta 2, accessory subunit) This gene encodes the 50-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. The encoded protein is required for the stimulation of DNA polymerase delta activity by the processivity cofactor proliferating cell nuclear antigen (PCNA). Expression of this gene may be a marker for ovarian carcinomas. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 5. [provided by RefSeq, Mar 2012]

POLD2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.285 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
POLD2	NM_006230.4	c.-56-101T>C		intron_variant		ENST00000610533.6	NP_006221.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
POLD2	ENST00000610533.6	c.-56-101T>C		intron_variant		1	NM_006230.4	ENSP00000480186.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36132 AN: 152034 Hom.: 4463 Cov.: 33

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.264

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.101

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.272

GnomAD4 exome AF: 0.256 AC: 328812 AN: 1284798 Hom.: 43308 Cov.: 33 AF XY: 0.252 AC XY: 156974 AN XY: 621802

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.297

Gnomad4 ASJ exome AF: 0.275

Gnomad4 EAS exome AF: 0.203

Gnomad4 SAS exome AF: 0.104

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.270

Gnomad4 OTH exome AF: 0.246

GnomAD4 genome AF: 0.238 AC: 36147 AN: 152152 Hom.: 4468 Cov.: 33 AF XY: 0.233 AC XY: 17302 AN XY: 74392

Gnomad4 AFR AF: 0.198

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.264

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.261

Gnomad4 OTH AF: 0.272

Alfa AF: 0.267 Hom.: 5511

Bravo AF: 0.248

Asia WGS AF: 0.163 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.9
DANN	Benign	0.61

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs3087370; hg19: chr7-44161809; COSMIC: COSV56262832; COSMIC: COSV56262832;