rs147478795

chr7-21744915-C-G

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.8362C>G(p.His2788Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000793 in 1,611,142 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (6 hom., cov: 33)
  • Exomes 𝑓: 0.00042 (6 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 4.00

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 (MetaRNN=0.0115222335).
• BP6: Variant 7-21744915-C-G is Benign according to our data. Variant chr7-21744915-C-G is described in ClinVar as [Benign]. Clinvar id is 238934.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00439 (669/152314) while in subpopulation AFR AF= 0.0153 (638/41564). AF 95% confidence interval is 0.0144. There are 6 homozygotes in gnomad4. There are 313 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.8362C>G	p.His2788Asp	missense_variant	51/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.8362C>G	p.His2788Asp	missense_variant	51/82	5	NM_001277115.2	P1
DNAH11	ENST00000605912.1	c.520C>G	p.His174Asp	missense_variant	4/4	3

Frequencies

GnomAD3 genomes AF: 0.00440 AC: 669 AN: 152196 Hom.: 6 Cov.: 33

Gnomad AFR AF: 0.0154

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.000939 AC: 229 AN: 243920 Hom.: 4 AF XY: 0.000644 AC XY: 85 AN XY: 132050

Gnomad AFR exome AF: 0.0144

Gnomad AMR exome AF: 0.000355

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000417 AC: 609 AN: 1458828 Hom.: 6 Cov.: 31 AF XY: 0.000325 AC XY: 236 AN XY: 725274

Gnomad4 AFR exome AF: 0.0162

Gnomad4 AMR exome AF: 0.000406

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: 0.000779

GnomAD4 genome AF: 0.00439 AC: 669 AN: 152314 Hom.: 6 Cov.: 33 AF XY: 0.00420 AC XY: 313 AN XY: 74490

Gnomad4 AFR AF: 0.0153

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000671 Hom.: 0

Bravo AF: 0.00481

ESP6500AA AF: 0.0146 AC: 58

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00125 AC: 151

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 02, 2018	- -

Primary ciliary dyskinesia Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Aug 17, 2015	This alteration is classified as 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 29, 2024	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 20, 2021

This variant is associated with the following publications: (PMID: 24450482) -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.40	T
BayesDel_noAF	Benign	-0.34
Cadd	Uncertain	24
Dann	Uncertain	0.99
Eigen	Uncertain	0.28
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	D;D;D;T
MetaRNN	Benign	0.012	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.53	T
Vest4		0.89
MVP		0.36
ClinPred		0.11	T
GERP RS		4.5
Varity_R		0.45
gMVP		0.48

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: rs147478795; hg19: chr7-21784533;