NM_005219.5:c.1848_1853dupTCCTCC

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_005219.5(DIAPH1):c.1848_1853dupTCCTCC(p.Pro617_Pro618dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0247 in 1,511,212 control chromosomes in the GnomAD database, including 190 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 42 hom., cov: 28)

Exomes 𝑓: 0.025 ( 148 hom. )

Consequence

DIAPH1
NM_005219.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 2.13

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 5-141573996-T-TGGAGGA is Benign according to our data. Variant chr5-141573996-T-TGGAGGA is described in ClinVar as [Likely_benign]. Clinvar id is 475698.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0239 (2998/125512) while in subpopulation EAS AF= 0.044 (191/4344). AF 95% confidence interval is 0.0389. There are 42 homozygotes in gnomad4. There are 1440 alleles in male gnomad4 subpopulation. Median coverage is 28. This position pass quality control queck.

BS2

High AC in GnomAd4 at 2998 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5 link	c.1848_1853dupTCCTCC	p.Pro617_Pro618dup	disruptive_inframe_insertion	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_1853dupTCCTCC	p.Pro617_Pro618dup	disruptive_inframe_insertion	Exon 16 of 28	5	NM_005219.5	ENSP00000373706.4	O60610-1
DIAPH1	ENST00000518047.5 link	c.1821_1826dupTCCTCC	p.Pro608_Pro609dup	disruptive_inframe_insertion	Exon 15 of 27	5		ENSP00000428268.2	O60610-3
DIAPH1	ENST00000647433.1 link	c.1848_1853dupTCCTCC	p.Pro617_Pro618dup	disruptive_inframe_insertion	Exon 16 of 29			ENSP00000494675.1	A0A2R8Y5N1
DIAPH1	ENST00000647330.1 link	n.1075_1080dupTCCTCC		downstream_gene_variant				ENSP00000494308.1	A0A2R8YEF8

Frequencies

GnomAD3 genomes

AF:

0.0239

AC:

2999

AN:

125442

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0121

Gnomad AMI

AF:

0.0274

Gnomad AMR

AF:

0.00990

Gnomad ASJ

AF:

0.00682

Gnomad EAS

AF:

0.0441

Gnomad SAS

AF:

0.0278

Gnomad FIN

AF:

0.0472

Gnomad MID

AF:

0.0310

Gnomad NFE

AF:

0.0298

Gnomad OTH

AF:

0.0131

GnomAD3 exomes

AF:

0.0287

AC:

2409

AN:

83800

Hom.:

AF XY:

0.0290

AC XY:

1267

AN XY:

43632

show subpopulations

Gnomad AFR exome

AF:

0.0167

Gnomad AMR exome

AF:

0.0134

Gnomad ASJ exome

AF:

0.00546

Gnomad EAS exome

AF:

0.0811

Gnomad SAS exome

AF:

0.0309

Gnomad FIN exome

AF:

0.0348

Gnomad NFE exome

AF:

0.0289

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0248

AC:

34385

AN:

1385700

Hom.:

148

Cov.:

AF XY:

0.0246

AC XY:

16823

AN XY:

683356

show subpopulations

Gnomad4 AFR exome

AF:

0.0133

Gnomad4 AMR exome

AF:

0.00737

Gnomad4 ASJ exome

AF:

0.00505

Gnomad4 EAS exome

AF:

0.0442

Gnomad4 SAS exome

AF:

0.0218

Gnomad4 FIN exome

AF:

0.0419

Gnomad4 NFE exome

AF:

0.0252

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.0239

AC:

2998

AN:

125512

Hom.:

Cov.:

AF XY:

0.0239

AC XY:

1440

AN XY:

60210

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.00989

Gnomad4 ASJ

AF:

0.00682

Gnomad4 EAS

AF:

0.0440

Gnomad4 SAS

AF:

0.0274

Gnomad4 FIN

AF:

0.0472

Gnomad4 NFE

AF:

0.0298

Gnomad4 OTH

AF:

0.0130

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Nov 07, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 28, 2017

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:3

Feb 09, 2017

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Pro608[15] in exon 16 of DIAPH1: This variant is not expected to have clinical significance because it has been identied in 1.2% (6/506) of East Asian chromos omes and 0.7% (51/7548) of European chromosomes by the Exome Aggregation Consort ium (ExAC, http://exac.broadinstitute.org; dbSNP rs374236039). -

Sep 08, 2016

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

Benign:1

Feb 04, 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