2-68654481-A-G

Position:

• chr2-68654481-A-G

Variant summary

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

The NM_138964.4(PROKR1):​c.486-399A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.587 in 151,980 control chromosomes in the GnomAD database, including 28,431 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 0.59 (28431 hom., cov: 31)
• Consequence: PROKR1 NM_138964.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116

Genes affected

PROKR1 (HGNC:4524): (prokineticin receptor 1) This gene encodes a member of the G-protein-coupled receptor family. The encoded protein binds to prokineticins (1 and 2), leading to the activation of MAPK and STAT signaling pathways. Prokineticins are protein ligands involved in angiogenesis and inflammation. The encoded protein is expressed in peripheral tissues such as those comprising the circulatory system, lungs, reproductive system, endocrine system and the gastrointestinal system. The protein may be involved in signaling in human fetal ovary during initiation of primordial follicle formation. Sequence variants in this gene may be associated with recurrent miscarriage. [provided by RefSeq, Aug 2016]

APLF (HGNC:28724): (aprataxin and PNKP like factor) Enables DNA-(apurinic or apyrimidinic site) endonuclease activity; nuclease activity; and nucleotide binding activity. Involved in double-strand break repair via nonhomologous end joining and single strand break repair. Acts upstream of or within positive regulation of DNA ligation. Located in nucleoplasm. Is active in site of double-strand break. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROKR1	NM_138964.4	c.486-399A>G		intron_variant		ENST00000303786.5	NP_620414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROKR1	ENST00000303786.5	c.486-399A>G		intron_variant		5	NM_138964.4	ENSP00000303775	P1
APLF	ENST00000627740.1	n.1198-399A>G		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.587 AC: 89159 AN: 151862 Hom.: 28366 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.405

Gnomad AMR AF: 0.483

Gnomad ASJ AF: 0.486

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.662

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.467

Gnomad OTH AF: 0.559

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.587 AC: 89285 AN: 151980 Hom.: 28431 Cov.: 31 AF XY: 0.588 AC XY: 43695 AN XY: 74270

Gnomad4 AFR AF: 0.849

Gnomad4 AMR AF: 0.483

Gnomad4 ASJ AF: 0.486

Gnomad4 EAS AF: 0.626

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.492

Gnomad4 NFE AF: 0.467

Gnomad4 OTH AF: 0.563

Alfa AF: 0.419 Hom.: 1556

Bravo AF: 0.592

Asia WGS AF: 0.665 AC: 2309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
DANN	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs6731838; hg19: chr2-68881613;