7-21543219-C-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6 BS1 BS2

The NM_001277115.2(DNAH11):c.-27C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,493,650 control chromosomes in the GnomAD database, including 148 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0084 (7 hom., cov: 33)
  • Exomes 𝑓: 0.014 (141 hom.)
• Consequence: DNAH11 NM_001277115.2 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:1
• Conservation: PhyloP100: -1.48

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]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 7-21543219-C-A is Benign according to our data. Variant chr7-21543219-C-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 359593.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1}.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0084 (1280/152318) while in subpopulation NFE AF= 0.0133 (904/68028). AF 95% confidence interval is 0.0126. There are 7 homozygotes in gnomad4. There are 584 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.-27C>A		5_prime_UTR_variant	1/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.-27C>A		5_prime_UTR_variant	1/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes AF: 0.00842 AC: 1282 AN: 152202 Hom.: 7 Cov.: 33

Gnomad AFR AF: 0.00314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0110

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00909 AC: 944 AN: 103860 Hom.: 7 AF XY: 0.00948 AC XY: 529 AN XY: 55820

Gnomad AFR exome AF: 0.00209

Gnomad AMR exome AF: 0.00806

Gnomad ASJ exome AF: 0.00806

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00548

Gnomad FIN exome AF: 0.000881

Gnomad NFE exome AF: 0.0152

Gnomad OTH exome AF: 0.0134

GnomAD4 exome AF: 0.0140 AC: 18745 AN: 1341332 Hom.: 141 Cov.: 30 AF XY: 0.0137 AC XY: 9007 AN XY: 657022

Gnomad4 AFR exome AF: 0.00165

Gnomad4 AMR exome AF: 0.00989

Gnomad4 ASJ exome AF: 0.00641

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00697

Gnomad4 FIN exome AF: 0.00118

Gnomad4 NFE exome AF: 0.0160

Gnomad4 OTH exome AF: 0.0141

GnomAD4 genome AF: 0.00840 AC: 1280 AN: 152318 Hom.: 7 Cov.: 33 AF XY: 0.00784 AC XY: 584 AN XY: 74478

Gnomad4 AFR AF: 0.00313

Gnomad4 AMR AF: 0.0109

Gnomad4 ASJ AF: 0.00547

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00662

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.0105 Hom.: 3

Bravo AF: 0.00956

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	5.2
Dann	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs72655966; hg19: chr7-21582837;