chr14-74863455-T-C
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
The NM_001243007.2(PROX2):āc.380A>Gā(p.Lys127Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00203 in 1,613,578 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.011 ( 31 hom., cov: 32)
Exomes š: 0.0011 ( 26 hom. )
Consequence
PROX2
NM_001243007.2 missense
NM_001243007.2 missense
Scores
6
10
Clinical Significance
Conservation
PhyloP100: 6.15
Genes affected
PROX2 (HGNC:26715): (prospero homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.0028780103).
BP6
Variant 14-74863455-T-C is Benign according to our data. Variant chr14-74863455-T-C is described in ClinVar as [Benign]. Clinvar id is 786621.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0111 (1689/152368) while in subpopulation AFR AF= 0.0379 (1576/41590). AF 95% confidence interval is 0.0363. There are 31 homozygotes in gnomad4. There are 793 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 31 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PROX2 | NM_001243007.2 | c.380A>G | p.Lys127Arg | missense_variant | 3/6 | ENST00000556489.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PROX2 | ENST00000556489.4 | c.380A>G | p.Lys127Arg | missense_variant | 3/6 | 1 | NM_001243007.2 | P1 | |
PROX2 | ENST00000673765.1 | c.380A>G | p.Lys127Arg | missense_variant | 3/5 |
Frequencies
GnomAD3 genomes AF: 0.0111 AC: 1685AN: 152250Hom.: 31 Cov.: 32
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GnomAD3 exomes AF: 0.00286 AC: 710AN: 248026Hom.: 11 AF XY: 0.00226 AC XY: 304AN XY: 134534
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GnomAD4 exome AF: 0.00108 AC: 1584AN: 1461210Hom.: 26 Cov.: 32 AF XY: 0.000975 AC XY: 709AN XY: 726860
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GnomAD4 genome AF: 0.0111 AC: 1689AN: 152368Hom.: 31 Cov.: 32 AF XY: 0.0106 AC XY: 793AN XY: 74512
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | May 18, 2018 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N
Sift
Uncertain
D;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at