dbSNP rs199864090: DNAH11:p.Val3750Gly (chr7-21861899-T-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001277115.2(DNAH11):c.11249T>G(p.Val3750Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000221 in 1,613,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:6B:1

Conservation

PhyloP100: 0.925

Publications

3 publications found

Variant links:

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]

DNAH11 Gene-Disease associations (from GenCC):

primary ciliary dyskinesia 7
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.015707612).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.11249T>G	p.Val3750Gly	missense	Exon 69 of 82	NP_001264044.1	Q96DT5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.11249T>G	p.Val3750Gly	missense	Exon 69 of 82	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1	TSL:4	n.432T>G		non_coding_transcript_exon	Exon 4 of 4
DNAH11	ENST00000607413.5	TSL:4	n.512T>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.000230

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000201

AC:

AN:

248410

AF XY:

0.000185

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.000204

Gnomad ASJ exome

AF:

0.00179

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000220

AC:

321

AN:

1461420

Hom.:

Cov.:

AF XY:

0.000208

AC XY:

151

AN XY:

726984

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

33466

American (AMR)

AF:

0.000201

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00226

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39686

South Asian (SAS)

AF:

0.00

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53384

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.000214

AC:

238

AN:

1111748

Other (OTH)

AF:

0.000166

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000230

AC:

AN:

152236

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41544

American (AMR)

AF:

0.000523

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.000272

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000357

AC:

ExAC

AF:

0.000157

AC:

EpiCase

AF:

0.000436

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Conflicting classifications of pathogenicity

Revision:criteria provided, conflicting classifications

View on ClinVar

Pathogenic

VUS

Benign

Condition

Primary ciliary dyskinesia (3)

Primary ciliary dyskinesia 7 (2)

not provided (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Benign

0.88

DEOGEN2

Benign

0.043

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.42

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.48

M_CAP

Benign

0.034

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.0

PhyloP100

0.93

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.4

REVEL

Benign

0.032

Sift

Benign

0.25

Vest4

0.21

MVP

0.41

ClinPred

0.023

GERP RS

0.39

Varity_R

0.060

gMVP

0.37

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over