rs386799737

Positions:

• chr17-80081958-CT-TG

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 2P and 8B. PM2 BP6_Very_Strong

The NM_017950.4(CCDC40):​c.1889_1890delCTinsTG​(p.Ala630Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Benignin Lovd. Synonymous variant affecting the same amino acid position (i.e. A630A) has been classified as Benign.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CCDC40 NM_017950.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.582

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP6: Variant 17-80081958-CT-TG is Benign according to our data. Variant chr17-80081958-CT-TG is described in ClinVar as [Benign]. Clinvar id is 215524.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.1889_1890delCTinsTG	p.Ala630Val	missense_variant		ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.1889_1890delCTinsTG	p.Ala630Val	missense_variant			NP_001230271.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.1889_1890delCTinsTG	p.Ala630Val	missense_variant		5	NM_017950.4	ENSP00000380679.4
CCDC40	ENST00000574799.5	n.1426_1427delCTinsTG		non_coding_transcript_exon_variant	8/16	1
CCDC40	ENST00000374877.7	c.1889_1890delCTinsTG	p.Ala630Val	missense_variant		5		ENSP00000364011.3
CCDC40	ENST00000572253.5	n.516_517delCTinsTG		non_coding_transcript_exon_variant	1/6	2

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	May 11, 2022	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs386799737; hg19: chr17-78055757;