rs187636110

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015512.5(DNAH1):c.2204G>A(p.Ser735Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00418 in 1,613,464 control chromosomes in the GnomAD database, including 29 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0032 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0043 ( 28 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.328

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=0.009891301).

BP6

Variant 3-52348985-G-A is Benign according to our data. Variant chr3-52348985-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478424.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00319 (486/152352) while in subpopulation NFE AF= 0.00491 (334/68038). AF 95% confidence interval is 0.00448. There are 1 homozygotes in gnomad4. There are 222 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.2204G>A	p.Ser735Asn	missense_variant	Exon 13 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.2204G>A	p.Ser735Asn	missense_variant	Exon 14 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.2204G>A	p.Ser735Asn	missense_variant	Exon 14 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.2204G>A	p.Ser735Asn	missense_variant	Exon 14 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 link	c.2204G>A	p.Ser735Asn	missense_variant	Exon 13 of 78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.2465G>A		non_coding_transcript_exon_variant	Exon 13 of 77	2
DNAH1	ENST00000497875.1 link	n.2369G>A		non_coding_transcript_exon_variant	Exon 14 of 21	2

Frequencies

GnomAD3 genomes

AF:

0.00319

AC:

486

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000675

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00491

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00413

AC:

1026

AN:

248688

Hom.:

AF XY:

0.00396

AC XY:

534

AN XY:

134944

show subpopulations

Gnomad AFR exome

AF:

0.000645

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000784

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.00647

Gnomad OTH exome

AF:

0.00347

GnomAD4 exome

AF:

0.00428

AC:

6251

AN:

1461112

Hom.:

Cov.:

AF XY:

0.00428

AC XY:

3114

AN XY:

726836

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000224

Gnomad4 ASJ exome

AF:

0.000612

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000499

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.00482

Gnomad4 OTH exome

AF:

0.00343

GnomAD4 genome

AF:

0.00319

AC:

486

AN:

152352

Hom.:

Cov.:

AF XY:

0.00298

AC XY:

222

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.000673

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00491

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00406

Hom.:

Bravo

AF:

0.00234

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00493

AC:

ESP6500AA

AF:

0.000921

AC:

ESP6500EA

AF:

0.00608

AC:

ExAC

AF:

0.00489

AC:

593

EpiCase

AF:

0.00305

EpiControl

AF:

0.00367

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 21, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH1: BP4, BS2 -

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

Benign:1

Jan 24, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.79

CADD

Benign

0.23

DANN

Benign

0.28

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.012

LIST_S2

Benign

0.43

MetaRNN

Benign

0.0099

MetaSVM

Benign

-0.96

PrimateAI

Benign

0.32

PROVEAN

Benign

-0.30

REVEL

Benign

0.051

Sift

Benign

0.52

Sift4G

Benign

0.51

Vest4

0.22

MVP

0.072

MPC

0.12

ClinPred

0.00079

GERP RS

2.8

gMVP

0.18

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