5-141573996-TGGAGGAGGAGGAGGAGGAGGA-TGGAGGAGGAGGAGGAGGAGGAGGA

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005219.5(DIAPH1):c.1851_1853dupTCC(p.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 0.0312 in 1,510,582 control chromosomes in the GnomAD database, including 343 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.046 ( 162 hom., cov: 28)

Exomes 𝑓: 0.030 ( 181 hom. )

Consequence

DIAPH1
NM_005219.5 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

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-TGGA is Benign according to our data. Variant chr5-141573996-T-TGGA is described in ClinVar as [Likely_benign]. Clinvar id is 226564.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.088 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DIAPH1	NM_005219.5 link	c.1851_1853dupTCC	p.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.1851_1853dupTCC	p.Pro618dup	disruptive_inframe_insertion	Exon 16 of 28	5	NM_005219.5	ENSP00000373706.4	O60610-1
DIAPH1	ENST00000518047.5 link	c.1824_1826dupTCC	p.Pro609dup	disruptive_inframe_insertion	Exon 15 of 27	5		ENSP00000428268.2	O60610-3
DIAPH1	ENST00000647433.1 link	c.1851_1853dupTCC	p.Pro618dup	disruptive_inframe_insertion	Exon 16 of 29			ENSP00000494675.1	A0A2R8Y5N1
DIAPH1	ENST00000647330.1 link	n.1078_1080dupTCC		downstream_gene_variant				ENSP00000494308.1	A0A2R8YEF8

Frequencies

GnomAD3 genomes

AF:

0.0457

AC:

5727

AN:

125396

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0908

Gnomad AMI

AF:

0.0835

Gnomad AMR

AF:

0.0300

Gnomad ASJ

AF:

0.0526

Gnomad EAS

AF:

0.0290

Gnomad SAS

AF:

0.0207

Gnomad FIN

AF:

0.00618

Gnomad MID

AF:

0.0310

Gnomad NFE

AF:

0.0311

Gnomad OTH

AF:

0.0369

GnomAD3 exomes

AF:

0.0450

AC:

3773

AN:

83800

Hom.:

AF XY:

0.0457

AC XY:

1996

AN XY:

43632

show subpopulations

Gnomad AFR exome

AF:

0.109

Gnomad AMR exome

AF:

0.0433

Gnomad ASJ exome

AF:

0.0676

Gnomad EAS exome

AF:

0.0539

Gnomad SAS exome

AF:

0.0450

Gnomad FIN exome

AF:

0.00691

Gnomad NFE exome

AF:

0.0407

Gnomad OTH exome

AF:

0.0536

GnomAD4 exome

AF:

0.0299

AC:

41374

AN:

1385114

Hom.:

181

Cov.:

AF XY:

0.0296

AC XY:

20243

AN XY:

683052

show subpopulations

Gnomad4 AFR exome

AF:

0.0799

Gnomad4 AMR exome

AF:

0.0248

Gnomad4 ASJ exome

AF:

0.0467

Gnomad4 EAS exome

AF:

0.0279

Gnomad4 SAS exome

AF:

0.0243

Gnomad4 FIN exome

AF:

0.00671

Gnomad4 NFE exome

AF:

0.0294

Gnomad4 OTH exome

AF:

0.0349

GnomAD4 genome

AF:

0.0457

AC:

5733

AN:

125468

Hom.:

162

Cov.:

AF XY:

0.0447

AC XY:

2693

AN XY:

60188

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.0300

Gnomad4 ASJ

AF:

0.0526

Gnomad4 EAS

AF:

0.0291

Gnomad4 SAS

AF:

0.0205

Gnomad4 FIN

AF:

0.00618

Gnomad4 NFE

AF:

0.0311

Gnomad4 OTH

AF:

0.0384

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Oct 31, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

c.1821TCC[12] in exon 16 of DIAPH1: This allele is a part of a poly TCC stretch and is not expected to have clinical significance because it has been identified in 3.1% (238/7732) of European American chromosomes and 6.7% (239/3592) of Afri can American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.wa shington.edu/EVS/; dbSNP rs35249032). -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 16, 2015

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:3

Apr 13, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 29, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 24, 2017

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

Significance: Likely benign

Review Status: criteria provided, single submitter

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