Variant 17-80090346-A-ACAC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_001243342.2(CCDC40):c.3040_3041insCAC(p.Thr1013dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0322 in 426,652 control chromosomes in the GnomAD database, including 945 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 68 hom., cov: 0)

Exomes 𝑓: 0.032 ( 877 hom. )

Consequence

CCDC40
NM_001243342.2 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.0180

Variant links:

Genes affected

CCDC40 (HGNC:26090): (coiled-coil domain 40 molecular ruler complex subunit) This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CCDC40 links:

CCDC40 (HGNC:):

CCDC40 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_001243342.2. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 17-80090346-A-ACAC is Benign according to our data. Variant chr17-80090346-A-ACAC is described in ClinVar as [Benign]. Clinvar id is 218550.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4 linkuse as main transcript	c.2832+462_2832+463insCAC		intron_variant		ENST00000397545.9	NP_060420.2	Q4G0X9-1
CCDC40	NM_001243342.2 linkuse as main transcript	c.3040_3041insCAC	p.Thr1013dup	disruptive_inframe_insertion	18/18		NP_001230271.1	Q4G0X9-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9 linkuse as main transcript	c.2832+462_2832+463insCAC		intron_variant		5	NM_017950.4	ENSP00000380679.4		Q4G0X9-1

Frequencies

GnomAD3 genomes

AF:

0.0294

AC:

567

AN:

19316

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0250

Gnomad AMI

AF:

0.0301

Gnomad AMR

AF:

0.0154

Gnomad ASJ

AF:

0.0185

Gnomad EAS

AF:

0.0219

Gnomad SAS

AF:

0.0649

Gnomad FIN

AF:

0.0576

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0362

Gnomad OTH

AF:

0.0167

GnomAD3 exomes

AF:

0.295

AC:

19150

AN:

65002

Hom.:

6216

AF XY:

0.320

AC XY:

11348

AN XY:

35428

show subpopulations

Gnomad AFR exome

AF:

0.0947

Gnomad AMR exome

AF:

0.196

Gnomad ASJ exome

AF:

0.468

Gnomad EAS exome

AF:

0.0957

Gnomad SAS exome

AF:

0.417

Gnomad FIN exome

AF:

0.495

Gnomad NFE exome

AF:

0.316

Gnomad OTH exome

AF:

0.284

GnomAD4 exome

AF:

0.0324

AC:

13186

AN:

407314

Hom.:

877

Cov.:

AF XY:

0.0333

AC XY:

6912

AN XY:

207388

show subpopulations

Gnomad4 AFR exome

AF:

0.0583

Gnomad4 AMR exome

AF:

0.0170

Gnomad4 ASJ exome

AF:

0.0485

Gnomad4 EAS exome

AF:

0.0100

Gnomad4 SAS exome

AF:

0.0387

Gnomad4 FIN exome

AF:

0.0447

Gnomad4 NFE exome

AF:

0.0309

Gnomad4 OTH exome

AF:

0.0356

GnomAD4 genome

AF:

0.0294

AC:

568

AN:

19338

Hom.:

Cov.:

AF XY:

0.0305

AC XY:

291

AN XY:

9548

show subpopulations

Gnomad4 AFR

AF:

0.0253

Gnomad4 AMR

AF:

0.0154

Gnomad4 ASJ

AF:

0.0185

Gnomad4 EAS

AF:

0.0219

Gnomad4 SAS

AF:

0.0659

Gnomad4 FIN

AF:

0.0576

Gnomad4 NFE

AF:

0.0361

Gnomad4 OTH

AF:

0.0164

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia	Feb 05, 2015	- -
Benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 28, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 14, 2019

- -

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