rs1546737

Variant names:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_015512.5(DNAH1):c.6957C>T(p.His2319His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.299 in 1,612,634 control chromosomes in the GnomAD database, including 75,624 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.24 ( 5629 hom., cov: 33)

Exomes 𝑓: 0.30 ( 69995 hom. )

Consequence

DNAH1
NM_015512.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.509

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 3-52373025-C-T is Benign according to our data. Variant chr3-52373025-C-T is described in ClinVar as [Benign]. Clinvar id is 402601.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.509 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.6957C>T	p.His2319His	synonymous_variant	Exon 44 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.7026C>T	p.His2342His	synonymous_variant	Exon 46 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.6957C>T	p.His2319His	synonymous_variant	Exon 45 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.7026C>T	p.His2342His	synonymous_variant	Exon 46 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH1	ENST00000420323.7 link	c.6957C>T	p.His2319His	synonymous_variant	Exon 44 of 78	1	NM_015512.5	ENSP00000401514.2		Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.7218C>T		non_coding_transcript_exon_variant	Exon 44 of 77	2

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36927

AN:

152112

Hom.:

5630

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0594

Gnomad AMI

AF:

0.330

Gnomad AMR

AF:

0.266

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.184

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.352

Gnomad MID

AF:

0.323

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.255

GnomAD3 exomes

AF:

0.287

AC:

71059

AN:

247388

Hom.:

11067

AF XY:

0.293

AC XY:

39377

AN XY:

134424

show subpopulations

Gnomad AFR exome

AF:

0.0516

Gnomad AMR exome

AF:

0.250

Gnomad ASJ exome

AF:

0.371

Gnomad EAS exome

AF:

0.167

Gnomad SAS exome

AF:

0.260

Gnomad FIN exome

AF:

0.362

Gnomad NFE exome

AF:

0.335

Gnomad OTH exome

AF:

0.307

GnomAD4 exome

AF:

0.305

AC:

445084

AN:

1460404

Hom.:

69995

Cov.:

AF XY:

0.305

AC XY:

221469

AN XY:

726510

show subpopulations

Gnomad4 AFR exome

AF:

0.0447

Gnomad4 AMR exome

AF:

0.252

Gnomad4 ASJ exome

AF:

0.371

Gnomad4 EAS exome

AF:

0.259

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.360

Gnomad4 NFE exome

AF:

0.317

Gnomad4 OTH exome

AF:

0.283

GnomAD4 genome

AF:

0.243

AC:

36930

AN:

152230

Hom.:

5629

Cov.:

AF XY:

0.244

AC XY:

18168

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0592

Gnomad4 AMR

AF:

0.266

Gnomad4 ASJ

AF:

0.362

Gnomad4 EAS

AF:

0.185

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.352

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.256

Alfa

AF:

0.309

Hom.:

9932

Bravo

AF:

0.224

Asia WGS

AF:

0.236

AC:

821

AN:

3478

EpiCase

AF:

0.332

EpiControl

AF:

0.330

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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

BayesDel_noAF

Benign

-0.31

CADD

Benign

4.5

DANN

Benign

0.92

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