Variant 7-21617753-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 6P and 1B. PM2PP3_StrongBP6

The NM_001277115.2(DNAH11):c.4230G>T(p.Trp1410Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000199 in 1,605,320 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 8.13

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.975

BP6

Variant 7-21617753-G-T is Benign according to our data. Variant chr7-21617753-G-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 219979.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Benign=1}.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.4230G>T	p.Trp1410Cys	missense_variant	23/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.4230G>T	p.Trp1410Cys	missense_variant	23/82	5	NM_001277115.2	ENSP00000475939.1		Q96DT5

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000125

AC:

AN:

240640

Hom.:

AF XY:

0.0000153

AC XY:

AN XY:

130568

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.00

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:

0.0000145

AC:

AN:

1453028

Hom.:

Cov.:

AF XY:

0.0000180

AC XY:

AN XY:

722236

show subpopulations

Gnomad4 AFR exome

AF:

0.000454

Gnomad4 AMR exome

AF:

0.0000234

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:

0.00

Gnomad4 OTH exome

AF:

0.0000834

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152292

Hom.:

Cov.:

AF XY:

0.000107

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000831

ExAC

AF:

0.00000827

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 03, 2024	The c.4230G>T (p.W1410C) alteration is located in exon 23 (coding exon 23) of the DNAH11 gene. This alteration results from a G to T substitution at nucleotide position 4230, causing the tryptophan (W) at amino acid position 1410 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 19, 2023	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.31

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.85

.;.;D

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.73

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.94

D;D;D

M_CAP

Uncertain

0.19

MetaRNN

Pathogenic

0.97

D;D;D

MetaSVM

Uncertain

0.29

PrimateAI

Uncertain

0.60

PROVEAN

Pathogenic

-11

.;D;.

REVEL

Pathogenic

0.83

Sift

Pathogenic

0.0

.;D;.

Vest4

0.84

MutPred

0.79

Loss of MoRF binding (P = 0.0152);Loss of MoRF binding (P = 0.0152);.;

MVP

0.82

ClinPred

1.0

GERP RS

5.6

Varity_R

0.95

gMVP

0.68

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over