rs878854439

chr7-21901172-A-ACATCTGGACCTTCAGGCTGAAGAGCGAAGAGAAGACTGCAAAATGGGTTCTGGCTGGAGTGGCTCTGCTTCTAGAAGCGTAAGGTAACACTGGCATTCCTCTAGCCTCTGCTGGAGTGCAGTGAGGATTTTCTAGCATGTTGCTGCACTGTTCC

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_Strong PM2

The NM_001277115.2(DNAH11):c.13473_*75dup variant causes a stop gained, frameshift 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 Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: DNAH11 NM_001277115.2 stop_gained, frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.41

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

CDCA7L (HGNC:30777): (cell division cycle associated 7 like) Acts upstream of or within positive regulation of cell population proliferation. Located in cytosol; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. There are 8 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.13473_*75dup		stop_gained, frameshift_variant	82/82	ENST00000409508.8
CDCA7L	NM_018719.5	c.*1149_*1150insGGAACAGTGCAGCAACATGCTAGAAAATCCTCACTGCACTCCAGCAGAGGCTAGAGGAATGCCAGTGTTACCTTACGCTTCTAGAAGCAGAGCCACTCCAGCCAGAACCCATTTTGCAGTCTTCTCTTCGCTCTTCAGCCTGAAGGTCCAGATG		3_prime_UTR_variant	10/10	ENST00000406877.8
CDCA7L	NM_001127370.3	c.*1149_*1150insGGAACAGTGCAGCAACATGCTAGAAAATCCTCACTGCACTCCAGCAGAGGCTAGAGGAATGCCAGTGTTACCTTACGCTTCTAGAAGCAGAGCCACTCCAGCCAGAACCCATTTTGCAGTCTTCTCTTCGCTCTTCAGCCTGAAGGTCCAGATG		3_prime_UTR_variant	11/11
CDCA7L	NM_001127371.3	c.*1149_*1150insGGAACAGTGCAGCAACATGCTAGAAAATCCTCACTGCACTCCAGCAGAGGCTAGAGGAATGCCAGTGTTACCTTACGCTTCTAGAAGCAGAGCCACTCCAGCCAGAACCCATTTTGCAGTCTTCTCTTCGCTCTTCAGCCTGAAGGTCCAGATG		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.13473_*75dup		stop_gained, frameshift_variant	82/82	5	NM_001277115.2	P1
CDCA7L	ENST00000406877.8	c.*1149_*1150insGGAACAGTGCAGCAACATGCTAGAAAATCCTCACTGCACTCCAGCAGAGGCTAGAGGAATGCCAGTGTTACCTTACGCTTCTAGAAGCAGAGCCACTCCAGCCAGAACCCATTTTGCAGTCTTCTCTTCGCTCTTCAGCCTGAAGGTCCAGATG		3_prime_UTR_variant	10/10	1	NM_018719.5	P1
CDCA7L	ENST00000356195.9	c.*1149_*1150insGGAACAGTGCAGCAACATGCTAGAAAATCCTCACTGCACTCCAGCAGAGGCTAGAGGAATGCCAGTGTTACCTTACGCTTCTAGAAGCAGAGCCACTCCAGCCAGAACCCATTTTGCAGTCTTCTCTTCGCTCTTCAGCCTGAAGGTCCAGATG		3_prime_UTR_variant	11/11	2
CDCA7L	ENST00000488845.1	n.1671_1672insGGAACAGTGCAGCAACATGCTAGAAAATCCTCACTGCACTCCAGCAGAGGCTAGAGGAATGCCAGTGTTACCTTACGCTTCTAGAAGCAGAGCCACTCCAGCCAGAACCCATTTTGCAGTCTTCTCTTCGCTCTTCAGCCTGAAGGTCCAGATG		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Invitae

Mar 08, 2016

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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: rs878854439; hg19: chr7-21940790;