7-21900080-G-C

Position:

• chr7-21900080-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001277115.2(DNAH11):​c.13263G>C​(p.Pro4421=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,828 control chromosomes in the GnomAD database, including 166 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. P4421P) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.010 (22 hom., cov: 33)
  • Exomes 𝑓: 0.011 (144 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.82

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BP6: Variant 7-21900080-G-C is Benign according to our data. Variant chr7-21900080-G-C is described in ClinVar as [Benign]. Clinvar id is 163129.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21900080-G-C is described in Lovd as [Likely_benign].
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0105 (1594/152240) while in subpopulation NFE AF= 0.0139 (945/68020). AF 95% confidence interval is 0.0132. There are 22 homozygotes in gnomad4. There are 853 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.13263G>C	p.Pro4421=	synonymous_variant	81/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.13263G>C	p.Pro4421=	synonymous_variant	81/82	5	NM_001277115.2	P1
DNAH11	ENST00000479878.1	n.634G>C		non_coding_transcript_exon_variant	4/5	3

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1594 AN: 152122 Hom.: 22 Cov.: 33

Gnomad AFR AF: 0.00225

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00740

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0377

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0139

Gnomad OTH AF: 0.00670

GnomAD3 exomes AF: 0.0110 AC: 2734 AN: 249016 Hom.: 36 AF XY: 0.0107 AC XY: 1451 AN XY: 135096

Gnomad AFR exome AF: 0.00175

Gnomad AMR exome AF: 0.00449

Gnomad ASJ exome AF: 0.00736

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000294

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.0139

Gnomad OTH exome AF: 0.0126

GnomAD4 exome AF: 0.0113 AC: 16548 AN: 1461588 Hom.: 144 Cov.: 31 AF XY: 0.0112 AC XY: 8115 AN XY: 727070

Gnomad4 AFR exome AF: 0.00134

Gnomad4 AMR exome AF: 0.00470

Gnomad4 ASJ exome AF: 0.00712

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000359

Gnomad4 FIN exome AF: 0.0363

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.00996

GnomAD4 genome AF: 0.0105 AC: 1594 AN: 152240 Hom.: 22 Cov.: 33 AF XY: 0.0115 AC XY: 853 AN XY: 74434

Gnomad4 AFR AF: 0.00224

Gnomad4 AMR AF: 0.00739

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0377

Gnomad4 NFE AF: 0.0139

Gnomad4 OTH AF: 0.00664

Alfa AF: 0.0108 Hom.: 16

Bravo AF: 0.00776

Asia WGS AF: 0.00202 AC: 7 AN: 3478

EpiCase AF: 0.0104

EpiControl AF: 0.00961

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	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Feb 21, 2013	Pro4421Pro in exon 81 of DNAH11: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 1.2% (101/8216) o f European American chromosomes from a broad population by the NHLBI Exome Seque ncing Project (http://evs.gs.washington.edu/EVS; dbSNP rs72658834). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Primary ciliary dyskinesia 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Oct 20, 2023

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

DNAH11: BP4, BP7, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	1.0
DANN	Benign	0.63

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: rs72658834; hg19: chr7-21939698;