chr2-68655083-A-C

Position:

• chr2-68655083-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4 BP6

The NM_138964.4(PROKR1):​c.689A>C​(p.Lys230Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PROKR1 NM_138964.4 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.38

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.30100167).
• BP6: Variant 2-68655083-A-C is Benign according to our data. Variant chr2-68655083-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 207838.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PROKR1	NM_138964.4	c.689A>C	p.Lys230Thr	missense_variant	3/3	ENST00000303786.5	NP_620414.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PROKR1	ENST00000303786.5	c.689A>C	p.Lys230Thr	missense_variant	3/3	5	NM_138964.4	ENSP00000303775	P1
APLF	ENST00000627740.1	n.1401A>C		non_coding_transcript_exon_variant	6/6	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

Long QT syndrome Benign:1

Likely benign, no assertion criteria provided

research

Medical Research Institute, Tokyo Medical and Dental University

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.61
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.47	.;T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Uncertain	0.96	D;.
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.30	T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.4	.;L
MutationTaster	Benign	0.55	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Uncertain	-3.8	D;D
REVEL	Benign	0.17
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0080	D;D
Polyphen		0.63	.;P
Vest4		0.57
MutPred		0.58		Loss of ubiquitination at K230 (P = 0.0155);Loss of ubiquitination at K230 (P = 0.0155);
MVP		0.099
MPC		0.43
ClinPred		0.98	D
GERP RS		2.2
Varity_R		0.43
gMVP		0.64

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: rs796052145; hg19: chr2-68882215;