rs144994507
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_144773.4(PROKR2):c.151G>A(p.Ala51Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00225 in 1,614,074 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_144773.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROKR2 | NM_144773.4 | c.151G>A | p.Ala51Thr | missense_variant | 2/3 | ENST00000678254.1 | |
PROKR2 | XM_017027646.2 | c.151G>A | p.Ala51Thr | missense_variant | 2/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROKR2 | ENST00000678254.1 | c.151G>A | p.Ala51Thr | missense_variant | 2/3 | NM_144773.4 | P1 | ||
PROKR2 | ENST00000217270.4 | c.151G>A | p.Ala51Thr | missense_variant | 2/3 | 1 | P1 | ||
PROKR2 | ENST00000678059.1 | c.43G>A | p.Ala15Thr | missense_variant | 2/3 |
Frequencies
GnomAD3 genomes ? AF: 0.00316 AC: 481AN: 152074Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.00449 AC: 1129AN: 251486Hom.: 15 AF XY: 0.00425 AC XY: 577AN XY: 135914
GnomAD4 exome AF: 0.00216 AC: 3158AN: 1461882Hom.: 25 Cov.: 34 AF XY: 0.00214 AC XY: 1558AN XY: 727244
GnomAD4 genome ? AF: 0.00316 AC: 481AN: 152192Hom.: 3 Cov.: 32 AF XY: 0.00417 AC XY: 310AN XY: 74418
ClinVar
Submissions by phenotype
not provided Benign:4
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) | - | - - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2022 | PROKR2: BP4, BS1, BS2 - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 30, 2015 | Lines of evidence used in support of classification: CANDIDATE: Alteration(s) of Potential Clinical Relevance Detected - |
not specified Benign:1
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Hypogonadotropic hypogonadism 3 with or without anosmia Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Mar 06, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at