chr7-21861927-C-G

Position:

chr7-21861927-C-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6

The NM_001277115.2(DNAH11):c.11277C>G(p.Ile3759Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,613,490 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/18 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 0.00063 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00070 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:3B:2

Conservation

PhyloP100: -0.00800

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:

DNAH11 (HGNC:):

DNAH11 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.014299542).

BP6

Variant 7-21861927-C-G is Benign according to our data. Variant chr7-21861927-C-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 238889.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Uncertain_significance=3}. Variant chr7-21861927-C-G is described in Lovd as [Likely_benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH11	NM_001277115.2 linkuse as main transcript	c.11277C>G	p.Ile3759Met	missense_variant	69/82	ENST00000409508.8	NP_001264044.1	Q96DT5Q96NT7H9NAJ8H9NAJ7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
DNAH11	ENST00000409508.8 linkuse as main transcript	c.11277C>G	p.Ile3759Met	missense_variant	69/82	5	NM_001277115.2	ENSP00000475939.1	Q96DT5
DNAH11	ENST00000421290.1 linkuse as main transcript	n.460C>G		non_coding_transcript_exon_variant	4/4	4
DNAH11	ENST00000607413.5 linkuse as main transcript	n.540C>G		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

152062

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.0462

Gnomad AMR

AF:

0.000131

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:

0.000720

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000310

AC:

AN:

248658

Hom.:

AF XY:

0.000267

AC XY:

AN XY:

134898

show subpopulations

Gnomad AFR exome

AF:

0.000129

Gnomad AMR exome

AF:

0.0000582

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.000594

Gnomad OTH exome

AF:

0.000830

GnomAD4 exome

AF:

0.000698

AC:

1020

AN:

1461428

Hom.:

Cov.:

AF XY:

0.000664

AC XY:

483

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.000209

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.000882

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000631

AC:

AN:

152062

Hom.:

Cov.:

AF XY:

0.000713

AC XY:

AN XY:

74288

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000558

Hom.:

Bravo

AF:

0.000824

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000243

AC:

ESP6500EA

AF:

0.000474

AC:

ExAC

AF:

0.000256

AC:

EpiCase

AF:

0.000873

EpiControl

AF:

0.000653

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:3Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Uncertain:1Benign:2

Uncertain significance, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Dec 08, 2021	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. -

Primary ciliary dyskinesia 7

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Jan 12, 2022

- -

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Jun 29, 2023

BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.44

CADD

Benign

8.9

DANN

Benign

0.88

DEOGEN2

Benign

0.081

.;.;T

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.65

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.44

T;T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.014

T;T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.24

PROVEAN

Benign

0.37

.;N;.

REVEL

Benign

0.062

Sift

Benign

0.057

.;T;.

Vest4

0.20

MVP

0.40

ClinPred

0.0068

GERP RS

1.6

Varity_R

0.056

gMVP

0.25

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