rs2289527

Variant names:

• chr17-80039925-G-A
• rs2289527
• NM_017950.4:c.207G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80039925-G-A
• chr17-80039925-G-C
• chr17-80039925-G-T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BP7

The ENST00000397545.9(CCDC40):​c.207G>A​(p.Val69Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. V69V) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CCDC40 ENST00000397545.9 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.77
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP7: Synonymous conserved (PhyloP=-2.77 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000397545.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	NM_017950.4	MANE Select	c.207G>A	p.Val69Val	synonymous	Exon 3 of 20	NP_060420.2
	CCDC40	NM_001243342.2		c.207G>A	p.Val69Val	synonymous	Exon 3 of 18	NP_001230271.1
	CCDC40	NM_001330508.2		c.207G>A	p.Val69Val	synonymous	Exon 3 of 11	NP_001317437.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC40	ENST00000397545.9	TSL:5 MANE Select	c.207G>A	p.Val69Val	synonymous	Exon 3 of 20	ENSP00000380679.4
	CCDC40	ENST00000374876.4	TSL:1	c.207G>A	p.Val69Val	synonymous	Exon 3 of 9	ENSP00000364010.4
	CCDC40	ENST00000374877.7	TSL:5	c.207G>A	p.Val69Val	synonymous	Exon 3 of 18	ENSP00000364011.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151780 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461648 Hom.: 0 Cov.: 40 AF XY: 0.00 AC XY: 0 AN XY: 727144

African (AFR) AF: 0.00 AC: 0 AN: 33476

American (AMR) AF: 0.00 AC: 0 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111784

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151780 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 74084

African (AFR) AF: 0.00 AC: 0 AN: 41282

American (AMR) AF: 0.00 AC: 0 AN: 15196

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10544

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2086

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.14
DANN	Benign	0.93
PhyloP100		-2.8

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2289527; hg19: chr17-78013724;