X-96738710-G-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_006729.5(DIAPH2):āc.290G>Cā(p.Arg97Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,095,696 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 22)
Exomes š: 0.0000082 ( 0 hom. 5 hem. )
Consequence
DIAPH2
NM_006729.5 missense
NM_006729.5 missense
Scores
1
7
9
Clinical Significance
Conservation
PhyloP100: 7.59
Genes affected
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 Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.15930983).
BS2
High Hemizygotes in GnomAdExome4 at 5 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DIAPH2 | NM_006729.5 | c.290G>C | p.Arg97Pro | missense_variant | 3/27 | ENST00000324765.13 | NP_006720.1 | |
DIAPH2 | NM_007309.4 | c.290G>C | p.Arg97Pro | missense_variant | 3/27 | NP_009293.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DIAPH2 | ENST00000324765.13 | c.290G>C | p.Arg97Pro | missense_variant | 3/27 | 1 | NM_006729.5 | ENSP00000321348 | A2 | |
DIAPH2 | ENST00000373049.8 | c.290G>C | p.Arg97Pro | missense_variant | 3/27 | 1 | ENSP00000362140 | P3 |
Frequencies
GnomAD3 genomes Cov.: 22
GnomAD3 genomes
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22
GnomAD3 exomes AF: 0.0000221 AC: 4AN: 180597Hom.: 0 AF XY: 0.0000306 AC XY: 2AN XY: 65295
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GnomAD4 exome AF: 0.00000821 AC: 9AN: 1095696Hom.: 0 Cov.: 29 AF XY: 0.0000138 AC XY: 5AN XY: 361256
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GnomAD4 genome Cov.: 22
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22
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 07, 2023 | The c.290G>C (p.R97P) alteration is located in exon 3 (coding exon 3) of the DIAPH2 gene. This alteration results from a G to C substitution at nucleotide position 290, causing the arginine (R) at amino acid position 97 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
.;.;.;T;T
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T;T
M_CAP
Uncertain
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
.;.;L;L;.
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.
REVEL
Uncertain
Sift
Benign
T;T;T;T;.
Sift4G
Benign
T;T;T;T;T
Polyphen
1.0, 0.13
.;.;D;B;.
Vest4
MutPred
Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP
MPC
0.47
ClinPred
T
GERP RS
Varity_R
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