rs759832724
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The ENST00000340635.11(PDE4D):c.2179C>T(p.Arg727Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,612,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R727Q) has been classified as Likely benign.
Frequency
Consequence
ENST00000340635.11 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PDE4D | NM_001104631.2 | c.2179C>T | p.Arg727Trp | missense_variant | 15/15 | ENST00000340635.11 | NP_001098101.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PDE4D | ENST00000340635.11 | c.2179C>T | p.Arg727Trp | missense_variant | 15/15 | 1 | NM_001104631.2 | ENSP00000345502 |
Frequencies
GnomAD3 genomes AF: 0.0000132 AC: 2AN: 152078Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248642Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134862
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1460610Hom.: 0 Cov.: 33 AF XY: 0.00000826 AC XY: 6AN XY: 726434
GnomAD4 genome AF: 0.0000132 AC: 2AN: 152078Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74274
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 13, 2021 | The c.2179C>T (p.R727W) alteration is located in exon 15 (coding exon 15) of the PDE4D gene. This alteration results from a C to T substitution at nucleotide position 2179, causing the arginine (R) at amino acid position 727 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Acrodysostosis 2 with or without hormone resistance Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Aug 07, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at