9-123382304-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_001352964.2(DENND1A):c.2341C>T(p.Arg781Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000261 in 1,610,816 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. R781L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001352964.2 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 |
---|---|---|---|---|---|---|---|
DENND1A | NM_001352964.2 | c.2341C>T | p.Arg781Cys | missense_variant | 24/24 | ENST00000394215.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DENND1A | ENST00000394215.7 | c.2341C>T | p.Arg781Cys | missense_variant | 24/24 | 5 | NM_001352964.2 | A2 | |
DENND1A | ENST00000473039.5 | n.2150C>T | non_coding_transcript_exon_variant | 18/18 | 1 | ||||
DENND1A | ENST00000373624.6 | c.2158C>T | p.Arg720Cys | missense_variant | 22/22 | 5 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000327 AC: 8AN: 244872Hom.: 0 AF XY: 0.0000376 AC XY: 5AN XY: 133122
GnomAD4 exome AF: 0.0000261 AC: 38AN: 1458512Hom.: 0 Cov.: 73 AF XY: 0.0000276 AC XY: 20AN XY: 725650
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74478
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 17, 2022 | The c.2158C>T (p.R720C) alteration is located in exon 22 (coding exon 22) of the DENND1A gene. This alteration results from a C to T substitution at nucleotide position 2158, causing the arginine (R) at amino acid position 720 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at