rs1187237772

chr12-48904954-GGCCAAGGAGGAACACAACAGT-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM4

The NM_033124.5(CCDC65):c.144_164del(p.Lys49_Ala55del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A48A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CCDC65 NM_033124.5 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.41

Genes affected

CCDC65 (HGNC:29937): (coiled-coil domain containing 65) This gene encodes a sperm tail protein that is highly expressed in adult testis, spermatocytes and spermatids. The protein plays a critical role in the assembly of the nexin-dynein regulatory complex. Mutations in this gene result in primary ciliary dyskinesia. [provided by RefSeq, Nov 2013]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_033124.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CCDC65	NM_033124.5	c.144_164del	p.Lys49_Ala55del	inframe_deletion	2/8	ENST00000320516.5
CCDC65	NM_001286957.2	c.-279-7_-266del		splice_acceptor_variant, 5_prime_UTR_variant, intron_variant	2/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CCDC65	ENST00000320516.5	c.144_164del	p.Lys49_Ala55del	inframe_deletion	2/8	1	NM_033124.5	P2
CCDC65	ENST00000266984.9	c.144_164del	p.Lys49_Ala55del	inframe_deletion	2/9	5		A2
CCDC65	ENST00000552942.5	c.144_164del	p.Lys49_Ala55del	inframe_deletion	2/6	5
CCDC65	ENST00000547861.5	c.111-7_124del		splice_acceptor_variant, coding_sequence_variant, intron_variant, NMD_transcript_variant	2/8	2

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia 27 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Oct 18, 2017

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acids is currently unknown. This variant has not been reported in the literature in individuals with CCDC65-related disease. This variant is not present in population databases (ExAC no frequency). This variant, c.144_164del, results in the deletion of 7 amino acids of the CCDC65 protein (p.Lys49_Ala55del), but otherwise preserves the integrity of the reading frame. -

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: rs1187237772; hg19: chr12-49298737;