rs3087370

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr7-44122210-A-C
• chr7-44122210-A-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000452185.5(POLD2):​c.-157T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000778 in 1,285,076 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 7.8e-7 (0 hom.)
• Consequence: POLD2 ENST00000452185.5 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: Uncertain_significance. The variant received 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
POLD2	NM_006230.4	c.-56-101T>G		intron_variant	Intron 1 of 10	ENST00000610533.6	NP_006221.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
POLD2	ENST00000610533.6	c.-56-101T>G		intron_variant	Intron 1 of 10	1	NM_006230.4	ENSP00000480186.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.78e-7 AC: 1 AN: 1285076 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 621918

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 28214

American (AMR) AF: 0.00 AC: 0 AN: 19606

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18902

East Asian (EAS) AF: 0.00 AC: 0 AN: 34444

South Asian (SAS) AF: 0.00 AC: 0 AN: 62054

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36954

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3592

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1028050

Other (OTH) AF: 0.0000188 AC: 1 AN: 53260

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	8.7
DANN	Benign	0.60
PhyloP100		0.24
PromoterAI		0.0032	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.22		Position offset: -15

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3087370; hg19: chr7-44161809;