rs72657339

Variant names:

• chr7-21698100-A-G
• rs72657339
• NM_001277115.2:c.6067A>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.6067A>G​(p.Ile2023Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,084 control chromosomes in the GnomAD database, including 36 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0019 (10 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (26 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 1.15

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=0.0039260983).
• BP6: Variant 7-21698100-A-G is Benign according to our data. Variant chr7-21698100-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 416437.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-21698100-A-G is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00188 (287/152294) while in subpopulation EAS AF= 0.0469 (243/5182). AF 95% confidence interval is 0.0421. There are 10 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.6067A>G	p.Ile2023Val	missense_variant	Exon 36 of 82	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.6067A>G	p.Ile2023Val	missense_variant	Exon 36 of 82	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.00189 AC: 288 AN: 152176 Hom.: 10 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0470

Gnomad SAS AF: 0.00310

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.00144

GnomAD3 exomes AF: 0.00352 AC: 873 AN: 248098 Hom.: 19 AF XY: 0.00323 AC XY: 434 AN XY: 134532

Gnomad AFR exome AF: 0.000518

Gnomad AMR exome AF: 0.0000585

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0461

Gnomad SAS exome AF: 0.000759

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.00183

GnomAD4 exome AF: 0.00105 AC: 1539 AN: 1460790 Hom.: 26 Cov.: 31 AF XY: 0.00103 AC XY: 747 AN XY: 726602

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0000674

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0295

Gnomad4 SAS exome AF: 0.00103

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000333

Gnomad4 OTH exome AF: 0.00380

GnomAD4 genome AF: 0.00188 AC: 287 AN: 152294 Hom.: 10 Cov.: 32 AF XY: 0.00219 AC XY: 163 AN XY: 74478

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0469

Gnomad4 SAS AF: 0.00311

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00150 Hom.: 7

Bravo AF: 0.00168

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.00104 AC: 4

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00353 AC: 426

Asia WGS AF: 0.0200 AC: 71 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:2

Aug 11, 2015

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 7 Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.064
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	13
DANN	Uncertain	1.0
DEOGEN2	Benign	0.062	.;.;T
Eigen	Benign	-0.065
Eigen_PC	Benign	0.085
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T;T;T
MetaRNN	Benign	0.0039	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-0.73	.;N;.
REVEL	Benign	0.058
Sift	Uncertain	0.0060	.;D;.
Vest4		0.29
MVP		0.13
ClinPred		0.027	T
GERP RS		5.3
Varity_R		0.080
gMVP		0.18

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: rs72657339; hg19: chr7-21737718; COSMIC: COSV60971973; COSMIC: COSV60971973;