rs143720019
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_015213.4(DENND5A):c.2129G>A(p.Arg710His) variant causes a missense change. The variant allele was found at a frequency of 0.0000385 in 1,612,452 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. R710C) has been classified as Uncertain significance.
Frequency
Consequence
NM_015213.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DENND5A | NM_015213.4 | c.2129G>A | p.Arg710His | missense_variant | 10/23 | ENST00000328194.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DENND5A | ENST00000328194.8 | c.2129G>A | p.Arg710His | missense_variant | 10/23 | 1 | NM_015213.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152198Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000517 AC: 13AN: 251370Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135850
GnomAD4 exome AF: 0.0000377 AC: 55AN: 1460254Hom.: 0 Cov.: 29 AF XY: 0.0000413 AC XY: 30AN XY: 726536
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152198Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74356
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 13, 2017 | Lines of evidence used in support of classification: UNCERTAIN: Alteration(s) of Uncertain Clinical Significance Detected - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 06, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 710 of the DENND5A protein (p.Arg710His). This variant is present in population databases (rs143720019, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with DENND5A-related conditions. ClinVar contains an entry for this variant (Variation ID: 520731). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at