GeneBe

rs1554208002

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_005219.5(DIAPH1):​c.2005T>C​(p.Leu669Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. L669L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 25)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DIAPH1
NM_005219.5 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0730

Publications

0 publications found
Variant links:
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 syndrome
    Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
  • autosomal dominant nonsyndromic hearing loss 1
    Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
  • progressive microcephaly-seizures-cortical blindness-developmental delay syndrome
    Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.63).
BP6
Variant 5-141573845-A-G is Benign according to our data. Variant chr5-141573845-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 542371.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.073 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DIAPH1NM_005219.5 linkc.2005T>C p.Leu669Leu synonymous_variant Exon 16 of 28 ENST00000389054.8 NP_005210.3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DIAPH1ENST00000389054.8 linkc.2005T>C p.Leu669Leu synonymous_variant Exon 16 of 28 5 NM_005219.5 ENSP00000373706.4
DIAPH1ENST00000518047.5 linkc.1978T>C p.Leu660Leu synonymous_variant Exon 15 of 27 5 ENSP00000428268.2
DIAPH1ENST00000647433.1 linkc.2005T>C p.Leu669Leu synonymous_variant Exon 16 of 29 ENSP00000494675.1
DIAPH1ENST00000647330.1 linkn.*1232T>C downstream_gene_variant ENSP00000494308.1

Frequencies

GnomAD3 genomes
Cov.:
25
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1375860
Hom.:
0
Cov.:
37
AF XY:
0.00
AC XY:
0
AN XY:
674172
African (AFR)
AF:
0.00
AC:
0
AN:
31964
American (AMR)
AF:
0.00
AC:
0
AN:
34660
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
22510
East Asian (EAS)
AF:
0.00
AC:
0
AN:
36654
South Asian (SAS)
AF:
0.00
AC:
0
AN:
73010
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
48312
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5534
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1066106
Other (OTH)
AF:
0.00
AC:
0
AN:
57110
GnomAD4 genome
Cov.:
25

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome Benign:1
Jul 05, 2022
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

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Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.63
CADD
Benign
2.1
DANN
Benign
0.77
PhyloP100
-0.073
RBP_binding_hub_radar
0.92
RBP_regulation_power_radar
2.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1554208002; hg19: chr5-140953412; API