rs200349268

Variant names:

• chr7-21789255-G-A
• rs200349268
• NM_001277115.2:c.9939G>A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Moderate BP6 BP7 BS2

The NM_001277115.2(DNAH11):​c.9939G>A​(p.Val3313Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000137 in 1,571,454 control chromosomes in the GnomAD database, including 3 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 0.00064 (3 hom., cov: 31)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: -0.0140

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.29).
• BP6: Variant 7-21789255-G-A is Benign according to our data. Variant chr7-21789255-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 257946.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.
• BP7: Synonymous conserved (PhyloP=-0.014 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.9939G>A	p.Val3313Val	synonymous_variant	Exon 61 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.9939G>A	p.Val3313Val	synonymous_variant	Exon 61 of 82	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.000645 AC: 98 AN: 152002 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.00189

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000852

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000192 AC: 36 AN: 187724 Hom.: 0 AF XY: 0.000171 AC XY: 17 AN XY: 99548

Gnomad AFR exome AF: 0.00251

Gnomad AMR exome AF: 0.0000724

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000741

Gnomad SAS exome AF: 0.000208

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000201

GnomAD4 exome AF: 0.0000824 AC: 117 AN: 1419334 Hom.: 0 Cov.: 30 AF XY: 0.0000827 AC XY: 58 AN XY: 701676

Gnomad4 AFR exome AF: 0.00200

Gnomad4 AMR exome AF: 0.0000521

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000266

Gnomad4 SAS exome AF: 0.000274

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000367

Gnomad4 OTH exome AF: 0.000390

GnomAD4 genome AF: 0.000644 AC: 98 AN: 152120 Hom.: 3 Cov.: 31 AF XY: 0.000457 AC XY: 34 AN XY: 74368

Gnomad4 AFR AF: 0.00188

Gnomad4 AMR AF: 0.000851

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000387

Gnomad4 SAS AF: 0.000623

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000454 Hom.: 6

Bravo AF: 0.000710

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:3

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Primary ciliary dyskinesia Uncertain:1 Benign:2

Dec 12, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 31, 2019

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.29
CADD	Benign	3.9
DANN	Benign	0.74

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: rs200349268; hg19: chr7-21828873; COSMIC: COSV105194065;