5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGA
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP3
The NM_005219.5(DIAPH1):c.1836_1853delTCCTCCTCCTCCTCCTCC(p.Pro613_Pro618del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000529 in 1,511,810 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.0000080 ( 0 hom., cov: 28)
Exomes 𝑓: 0.0000050 ( 0 hom. )
Consequence
DIAPH1
NM_005219.5 disruptive_inframe_deletion
NM_005219.5 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 4.53
Publications
2 publications found
Genes affected
DIAPH1 (HGNC:2876): (diaphanous related formin 1) This gene is a homolog of the Drosophila diaphanous gene, and has been linked to autosomal dominant, fully penetrant, nonsyndromic sensorineural progressive low-frequency hearing loss. Actin polymerization involves proteins known to interact with diaphanous protein in Drosophila and mouse. It has therefore been speculated that this gene may have a role in the regulation of actin polymerization in hair cells of the inner ear. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
DIAPH1 Gene-Disease associations (from GenCC):
- DIAPH1-related sensorineural hearing loss-thrombocytopenia syndromeInheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- autosomal dominant nonsyndromic hearing loss 1Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
- progressive microcephaly-seizures-cortical blindness-developmental delay syndromeInheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -1 ACMG points.
BP3
Nonframeshift variant in repetitive region in NM_005219.5
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| DIAPH1 | ENST00000389054.8 | c.1836_1853delTCCTCCTCCTCCTCCTCC | p.Pro613_Pro618del | disruptive_inframe_deletion | Exon 16 of 28 | 5 | NM_005219.5 | ENSP00000373706.4 | ||
| DIAPH1 | ENST00000518047.5 | c.1809_1826delTCCTCCTCCTCCTCCTCC | p.Pro604_Pro609del | disruptive_inframe_deletion | Exon 15 of 27 | 5 | ENSP00000428268.2 | |||
| DIAPH1 | ENST00000647433.1 | c.1836_1853delTCCTCCTCCTCCTCCTCC | p.Pro613_Pro618del | disruptive_inframe_deletion | Exon 16 of 29 | ENSP00000494675.1 | ||||
| DIAPH1 | ENST00000647330.1 | n.*1063_*1080delTCCTCCTCCTCCTCCTCC | downstream_gene_variant | ENSP00000494308.1 |
Frequencies
GnomAD3 genomes 0.00000797 AC: 1AN: 125476Hom.: 0 Cov.: 28 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
125476
Hom.:
Cov.:
28
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000505 AC: 7AN: 1386334Hom.: 0 AF XY: 0.00000585 AC XY: 4AN XY: 683650 show subpopulations
GnomAD4 exome
AF:
AC:
7
AN:
1386334
Hom.:
AF XY:
AC XY:
4
AN XY:
683650
show subpopulations
African (AFR)
AF:
AC:
0
AN:
31388
American (AMR)
AF:
AC:
0
AN:
35304
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
24734
East Asian (EAS)
AF:
AC:
0
AN:
35360
South Asian (SAS)
AF:
AC:
3
AN:
77860
European-Finnish (FIN)
AF:
AC:
0
AN:
47518
Middle Eastern (MID)
AF:
AC:
0
AN:
4444
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1072274
Other (OTH)
AF:
AC:
0
AN:
57452
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
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4
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<30
30-35
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>80
Age
GnomAD4 genome 0.00000797 AC: 1AN: 125476Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0AN XY: 60152 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
1
AN:
125476
Hom.:
Cov.:
28
AF XY:
AC XY:
0
AN XY:
60152
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32940
American (AMR)
AF:
AC:
0
AN:
12422
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3078
East Asian (EAS)
AF:
AC:
0
AN:
4354
South Asian (SAS)
AF:
AC:
0
AN:
3778
European-Finnish (FIN)
AF:
AC:
0
AN:
7764
Middle Eastern (MID)
AF:
AC:
0
AN:
226
European-Non Finnish (NFE)
AF:
AC:
1
AN:
58434
Other (OTH)
AF:
AC:
0
AN:
1676
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.375
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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