rs56002041

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015512.5(DNAH1):c.7151A>G(p.Asn2384Ser) variant causes a missense change. The variant allele was found at a frequency of 0.109 in 1,612,530 control chromosomes in the GnomAD database, including 10,807 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 616 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10191 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 3.77

Variant links:

Genes affected

DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

DNAH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0019221604).

BP6

Variant 3-52375405-A-G is Benign according to our data. Variant chr3-52375405-A-G is described in ClinVar as [Benign]. Clinvar id is 402602.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.7151A>G	p.Asn2384Ser	missense_variant	Exon 45 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.7220A>G	p.Asn2407Ser	missense_variant	Exon 47 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.7151A>G	p.Asn2384Ser	missense_variant	Exon 46 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.7220A>G	p.Asn2407Ser	missense_variant	Exon 47 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 link	c.7151A>G	p.Asn2384Ser	missense_variant	Exon 45 of 78	1	NM_015512.5	ENSP00000401514.2		Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.7412A>G		non_coding_transcript_exon_variant	Exon 45 of 77	2

Frequencies

GnomAD3 genomes

AF:

0.0779

AC:

11851

AN:

152166

Hom.:

617

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0200

Gnomad AMI

AF:

0.0713

Gnomad AMR

AF:

0.0742

Gnomad ASJ

AF:

0.126

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0660

Gnomad FIN

AF:

0.0526

Gnomad MID

AF:

0.120

Gnomad NFE

AF:

0.121

Gnomad OTH

AF:

0.102

GnomAD3 exomes

AF:

0.0836

AC:

20628

AN:

246688

Hom.:

1040

AF XY:

0.0848

AC XY:

11357

AN XY:

133862

show subpopulations

Gnomad AFR exome

AF:

0.0179

Gnomad AMR exome

AF:

0.0634

Gnomad ASJ exome

AF:

0.119

Gnomad EAS exome

AF:

0.000279

Gnomad SAS exome

AF:

0.0720

Gnomad FIN exome

AF:

0.0566

Gnomad NFE exome

AF:

0.117

Gnomad OTH exome

AF:

0.0913

GnomAD4 exome

AF:

0.112

AC:

163898

AN:

1460246

Hom.:

10191

Cov.:

AF XY:

0.111

AC XY:

80613

AN XY:

726340

show subpopulations

Gnomad4 AFR exome

AF:

0.0188

Gnomad4 AMR exome

AF:

0.0663

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.000328

Gnomad4 SAS exome

AF:

0.0751

Gnomad4 FIN exome

AF:

0.0593

Gnomad4 NFE exome

AF:

0.127

Gnomad4 OTH exome

AF:

0.105

GnomAD4 genome

AF:

0.0778

AC:

11847

AN:

152284

Hom.:

616

Cov.:

AF XY:

0.0751

AC XY:

5592

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0200

Gnomad4 AMR

AF:

0.0741

Gnomad4 ASJ

AF:

0.126

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0667

Gnomad4 FIN

AF:

0.0526

Gnomad4 NFE

AF:

0.121

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.113

Hom.:

1497

Bravo

AF:

0.0763

TwinsUK

AF:

0.130

AC:

483

ALSPAC

AF:

0.127

AC:

491

ESP6500AA

AF:

0.0183

AC:

ESP6500EA

AF:

0.122

AC:

1026

ExAC

AF:

0.0828

AC:

10023

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Benign

0.67

Eigen

Benign

-0.99

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.053

LIST_S2

Benign

0.73

MetaRNN

Benign

0.0019

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.28

PROVEAN

Benign

1.0

REVEL

Benign

0.059

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.052

MPC

0.098

ClinPred

0.0017

GERP RS

2.9

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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