X-96884682-T-C
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The ENST00000324765.13(DIAPH2):c.587+2964T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000024 in 1,208,159 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 10 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 21)
Exomes 𝑓: 0.000024 ( 0 hom. 9 hem. )
Consequence
DIAPH2
ENST00000324765.13 intron
ENST00000324765.13 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.0630
Genes affected
RPA4 (HGNC:30305): (replication protein A4) This gene encodes a single-stranded DNA-binding protein that is the 30-kDa subunit of the replication protein A complex. Replication protein A is an essential factor for DNA double-strand break repair and cell cycle checkpoint activation. The encoded protein localizes to DNA repair foci and may be involved in the cellular DNA damage response. This protein may also play a role in inhibiting viral replication.[provided by RefSeq, Apr 2010]
DIAPH2 (HGNC:2877): (diaphanous related formin 2) The product of this gene belongs to the diaphanous subfamily of the formin homology family of proteins. This gene may play a role in the development and normal function of the ovaries. Defects in this gene have been linked to premature ovarian failure 2. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.98).
BP6
Variant X-96884682-T-C is Benign according to our data. Variant chrX-96884682-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2661023.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 9 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RPA4 | NM_013347.4 | c.372T>C | p.Tyr124= | synonymous_variant | 1/1 | ENST00000373040.4 | NP_037479.1 | |
DIAPH2 | NM_006729.5 | c.587+2964T>C | intron_variant | ENST00000324765.13 | NP_006720.1 | |||
DIAPH2 | NM_007309.4 | c.587+2964T>C | intron_variant | NP_009293.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RPA4 | ENST00000373040.4 | c.372T>C | p.Tyr124= | synonymous_variant | 1/1 | NM_013347.4 | ENSP00000362131 | P1 | ||
DIAPH2 | ENST00000324765.13 | c.587+2964T>C | intron_variant | 1 | NM_006729.5 | ENSP00000321348 | A2 | |||
DIAPH2 | ENST00000373049.8 | c.587+2964T>C | intron_variant | 1 | ENSP00000362140 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000272 AC: 3AN: 110173Hom.: 0 Cov.: 21 AF XY: 0.0000309 AC XY: 1AN XY: 32389
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GnomAD3 exomes AF: 0.0000109 AC: 2AN: 183086Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 67626
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GnomAD4 exome AF: 0.0000237 AC: 26AN: 1097986Hom.: 0 Cov.: 31 AF XY: 0.0000248 AC XY: 9AN XY: 363346
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GnomAD4 genome AF: 0.0000272 AC: 3AN: 110173Hom.: 0 Cov.: 21 AF XY: 0.0000309 AC XY: 1AN XY: 32389
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | RPA4: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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