rs1554294478

Positions:

• chr7-21901224-GGCTGGAGTGGCTCTGCTTCTAGAAGCGTAAGGTAACACTGGCATTCCTCTAGCCTCT-G

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PM4 PP5

The NM_001277115.2(DNAH11):​c.13531_*36del variant causes a stop lost, 3 prime UTR change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,178 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars). Synonymous variant affecting the same amino acid position (i.e. A4508A) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAH11 NM_001277115.2 stop_lost, 3_prime_UTR
• Clinical Significance: Pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 7.77

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 Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_001277115.2 Downstream stopcodon found after 55 codons.
• PP5: Variant 7-21901224-GGCTGGAGTGGCTCTGCTTCTAGAAGCGTAAGGTAACACTGGCATTCCTCTAGCCTCT-G is Pathogenic according to our data. Variant chr7-21901224-GGCTGGAGTGGCTCTGCTTCTAGAAGCGTAAGGTAACACTGGCATTCCTCTAGCCTCT-G is described in ClinVar as [Pathogenic]. Clinvar id is 6476.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.13531_*36del		stop_lost, 3_prime_UTR_variant	82/82	ENST00000409508.8
CDCA7L	NM_018719.5	c.*1041_*1097del		3_prime_UTR_variant	10/10	ENST00000406877.8
CDCA7L	NM_001127370.3	c.*1041_*1097del		3_prime_UTR_variant	11/11
CDCA7L	NM_001127371.3	c.*1041_*1097del		3_prime_UTR_variant	9/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CDCA7L	ENST00000406877.8	c.*1041_*1097del		3_prime_UTR_variant	10/10	1	NM_018719.5	P1
DNAH11	ENST00000409508.8	c.13531_*36del		stop_lost, 3_prime_UTR_variant	82/82	5	NM_001277115.2	P1
CDCA7L	ENST00000356195.9	c.*1041_*1097del		3_prime_UTR_variant	11/11	2
CDCA7L	ENST00000488845.1	n.1563_1619del		non_coding_transcript_exon_variant	4/4	2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461178 Hom.: 0 AF XY: 0.00000275 AC XY: 2 AN XY: 726864

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Primary ciliary dyskinesia 7 Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Feb 01, 2008

- -

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: rs1554294478; hg19: chr7-21940842;