rs72658832

Positions:

• chr7-21899961-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001277115.2(DNAH11):​c.13163-19T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00407 in 1,612,826 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0032 (2 hom., cov: 33)
  • Exomes 𝑓: 0.0042 (28 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.534

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 7-21899961-T-A is Benign according to our data. Variant chr7-21899961-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 257869.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00321 (488/152240) while in subpopulation SAS AF= 0.0085 (41/4826). AF 95% confidence interval is 0.00644. There are 2 homozygotes in gnomad4. There are 238 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.13163-19T>A		intron_variant		ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.13163-19T>A		intron_variant		5	NM_001277115.2	P1
DNAH11	ENST00000479878.1	n.534-19T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.00321 AC: 489 AN: 152122 Hom.: 2 Cov.: 33

Gnomad AFR AF: 0.000459

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00386

Gnomad ASJ AF: 0.00778

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00468

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.00422 AC: 1045 AN: 247470 Hom.: 8 AF XY: 0.00475 AC XY: 638 AN XY: 134258

Gnomad AFR exome AF: 0.000584

Gnomad AMR exome AF: 0.00363

Gnomad ASJ exome AF: 0.00793

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00846

Gnomad FIN exome AF: 0.00121

Gnomad NFE exome AF: 0.00470

Gnomad OTH exome AF: 0.00383

GnomAD4 exome AF: 0.00416 AC: 6082 AN: 1460586 Hom.: 28 Cov.: 31 AF XY: 0.00445 AC XY: 3232 AN XY: 726542

Gnomad4 AFR exome AF: 0.000629

Gnomad4 AMR exome AF: 0.00362

Gnomad4 ASJ exome AF: 0.00897

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00794

Gnomad4 FIN exome AF: 0.00137

Gnomad4 NFE exome AF: 0.00419

Gnomad4 OTH exome AF: 0.00338

GnomAD4 genome AF: 0.00321 AC: 488 AN: 152240 Hom.: 2 Cov.: 33 AF XY: 0.00320 AC XY: 238 AN XY: 74434

Gnomad4 AFR AF: 0.000458

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00778

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00850

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.00468

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00418 Hom.: 1

Bravo AF: 0.00346

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 30, 2015	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Aug 28, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.20
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs72658832; hg19: chr7-21939579;