NM_005219.5:c.1848_1853delTCCTCC

Variant names:

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_005219.5(DIAPH1):c.1848_1853delTCCTCC(p.Pro617_Pro618del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000591 in 1,511,370 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00088 ( 0 hom., cov: 28)

Exomes 𝑓: 0.00057 ( 1 hom. )

Consequence

DIAPH1
NM_005219.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:4

Conservation

PhyloP100: 4.53

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 5-141573996-TGGAGGA-T is Benign according to our data. Variant chr5-141573996-TGGAGGA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 351294.We mark this variant Likely_benign, oryginal submissions are: {Benign=4, Uncertain_significance=1}. Variant chr5-141573996-TGGAGGA-T is described in Lovd as [Likely_benign]. Variant chr5-141573996-TGGAGGA-T is described in Lovd as [Likely_benign]. Variant chr5-141573996-TGGAGGA-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000876 (110/125546) while in subpopulation EAS AF= 0.00967 (42/4344). AF 95% confidence interval is 0.00735. There are 0 homozygotes in gnomad4. There are 57 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High AC in GnomAd4 at 110 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5 link	c.1848_1853delTCCTCC	p.Pro617_Pro618del	disruptive_inframe_deletion	Exon 16 of 28	ENST00000389054.8	NP_005210.3	O60610-1Q6URC4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DIAPH1	ENST00000389054.8 link	c.1848_1853delTCCTCC	p.Pro617_Pro618del	disruptive_inframe_deletion	Exon 16 of 28	5	NM_005219.5	ENSP00000373706.4	O60610-1
DIAPH1	ENST00000518047.5 link	c.1821_1826delTCCTCC	p.Pro608_Pro609del	disruptive_inframe_deletion	Exon 15 of 27	5		ENSP00000428268.2	O60610-3
DIAPH1	ENST00000647433.1 link	c.1848_1853delTCCTCC	p.Pro617_Pro618del	disruptive_inframe_deletion	Exon 16 of 29			ENSP00000494675.1	A0A2R8Y5N1
DIAPH1	ENST00000647330.1 link	n.1075_1080delTCCTCC		downstream_gene_variant				ENSP00000494308.1	A0A2R8YEF8

Frequencies

GnomAD3 genomes

AF:

0.000885

AC:

111

AN:

125476

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000805

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00965

Gnomad SAS

AF:

0.00371

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00442

Gnomad NFE

AF:

0.000240

Gnomad OTH

AF:

0.00179

GnomAD3 exomes

AF:

0.00248

AC:

208

AN:

83800

Hom.:

AF XY:

0.00241

AC XY:

105

AN XY:

43632

show subpopulations

Gnomad AFR exome

AF:

0.00124

Gnomad AMR exome

AF:

0.000720

Gnomad ASJ exome

AF:

0.000405

Gnomad EAS exome

AF:

0.0177

Gnomad SAS exome

AF:

0.00542

Gnomad FIN exome

AF:

0.000596

Gnomad NFE exome

AF:

0.000678

Gnomad OTH exome

AF:

0.00218

GnomAD4 exome

AF:

0.000565

AC:

783

AN:

1385824

Hom.:

AF XY:

0.000623

AC XY:

426

AN XY:

683432

show subpopulations

Gnomad4 AFR exome

AF:

0.000669

Gnomad4 AMR exome

AF:

0.000312

Gnomad4 ASJ exome

AF:

0.000284

Gnomad4 EAS exome

AF:

0.00701

Gnomad4 SAS exome

AF:

0.00263

Gnomad4 FIN exome

AF:

0.000168

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.00111

GnomAD4 genome

AF:

0.000876

AC:

110

AN:

125546

Hom.:

Cov.:

AF XY:

0.000946

AC XY:

AN XY:

60230

show subpopulations

Gnomad4 AFR

AF:

0.000817

Gnomad4 AMR

AF:

0.000804

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00967

Gnomad4 SAS

AF:

0.00372

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000240

Gnomad4 OTH

AF:

0.00177

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:4

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DIAPH1: BS1, BS2 -

Nonsyndromic Hearing Loss, Mixed

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Aug 23, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Pro619_Pro620del in exon 16 of DIAPH1: This variant is not expected to have cl inical significance because it has been identified in 2.77% (14/506) of East Asi an chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs760344729). -

Autosomal dominant nonsyndromic hearing loss 1;C5567650:Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome

Benign:1

Jan 22, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over