7-44122210-A-G

Variant names:

• chr7-44122210-A-G
• rs3087370
• ENST00000452185.5:c.-157T>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 17 publications found

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 Gene-Disease associations (from GenCC):

• non-severe combined immunodeficiency due to polymerase delta deficiency

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001127218.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLD2	NM_006230.4	MANE Select	c.-56-101T>C		intron	N/A	NP_006221.3
	POLD2	NM_001127218.3		c.-157T>C		5_prime_UTR	Exon 2 of 11	NP_001120690.1
	POLD2	NM_001256879.2		c.-142-15T>C		intron	N/A	NP_001243808.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLD2	ENST00000452185.5	TSL:1	c.-157T>C		5_prime_UTR	Exon 2 of 11	ENSP00000395231.1
	POLD2	ENST00000610533.6	TSL:1 MANE Select	c.-56-101T>C		intron	N/A	ENSP00000480186.2
	POLD2	ENST00000964235.1		c.-157T>C		5_prime_UTR	Exon 2 of 11	ENSP00000634294.1

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

African (AFR) AF: 0.185 AC: 5230 AN: 28214

American (AMR) AF: 0.297 AC: 5824 AN: 19588

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 5191 AN: 18894

East Asian (EAS) AF: 0.203 AC: 6977 AN: 34432

South Asian (SAS) AF: 0.104 AC: 6450 AN: 62044

European-Finnish (FIN) AF: 0.208 AC: 7689 AN: 36932

Middle Eastern (MID) AF: 0.219 AC: 785 AN: 3592

European-Non Finnish (NFE) AF: 0.270 AC: 277545 AN: 1027856

Other (OTH) AF: 0.246 AC: 13121 AN: 53246

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

African (AFR) AF: 0.198 AC: 8224 AN: 41520

American (AMR) AF: 0.292 AC: 4460 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.264 AC: 916 AN: 3468

East Asian (EAS) AF: 0.233 AC: 1207 AN: 5178

South Asian (SAS) AF: 0.102 AC: 492 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2105 AN: 10586

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.261 AC: 17771 AN: 67984

Other (OTH) AF: 0.272 AC: 573 AN: 2108

Alfa AF: 0.264 Hom.: 7087

Bravo AF: 0.248

Asia WGS AF: 0.163 AC: 569 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.9
DANN	Benign	0.61
PhyloP100		0.24
PromoterAI		-0.028	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3087370; hg19: chr7-44161809; COSMIC: COSV56262832; COSMIC: COSV56262832;