chr11-27340785-TCTGCTATTTCCTTTTTCTC-T

Position:

• chr11-27340785-TCTGCTATTTCCTTTTTCTC-T

Variant summary

Our verdict is Likely pathogenic. Variant got 7 ACMG points: 7P and 0B. PVS1_Strong PM2 PP5

The NM_030771.2(CCDC34):​c.799_817delGAGAAAAAGGAAATAGCAG​(p.Glu267fs) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 33)
• Consequence: CCDC34 NM_030771.2 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.37

Genes affected

CCDC34 (HGNC:25079): (coiled-coil domain containing 34)

ACMG classification

Verdict is Likely_pathogenic. Variant got 7 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most 50 bp of the penultimate exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.288 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 11-27340785-TCTGCTATTTCCTTTTTCTC-T is Pathogenic according to our data. Variant chr11-27340785-TCTGCTATTTCCTTTTTCTC-T is described in ClinVar as [Pathogenic]. Clinvar id is 1710910.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr11-27340785-TCTGCTATTTCCTTTTTCTC-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC34	NM_030771.2	c.799_817delGAGAAAAAGGAAATAGCAG	p.Glu267fs	frameshift_variant	5/6	ENST00000328697.11	NP_110398.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC34	ENST00000328697.11	c.799_817delGAGAAAAAGGAAATAGCAG	p.Glu267fs	frameshift_variant	5/6	1	NM_030771.2	ENSP00000330240.5
CCDC34	ENST00000529615.1	n.286_304delGAGAAAAAGGAAATAGCAG		non_coding_transcript_exon_variant	3/6	3

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Spermatogenic failure 76 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Oct 17, 2022

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27362332;