3-52386299-C-T

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.8765C>T(p.Ala2922Val) variant causes a missense change. The variant allele was found at a frequency of 0.00323 in 1,601,892 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0033 ( 10 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.97

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=0.014848143).

BP6

Variant 3-52386299-C-T is Benign according to our data. Variant chr3-52386299-C-T is described in ClinVar as [Benign]. Clinvar id is 478504.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-52386299-C-T is described in Lovd as [Likely_benign]. Variant chr3-52386299-C-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00214 (326/152364) while in subpopulation NFE AF= 0.00401 (273/68030). AF 95% confidence interval is 0.00362. There are 0 homozygotes in gnomad4. There are 136 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH1	NM_015512.5 link	c.8765C>T	p.Ala2922Val	missense_variant	Exon 55 of 78	ENST00000420323.7	NP_056327.4	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006129.2 link	c.8834C>T	p.Ala2945Val	missense_variant	Exon 57 of 80		XP_016861618.1
DNAH1	XM_017006130.2 link	c.8765C>T	p.Ala2922Val	missense_variant	Exon 56 of 79		XP_016861619.1	Q9P2D7-4A0A140VJI6
DNAH1	XM_017006131.2 link	c.8834C>T	p.Ala2945Val	missense_variant	Exon 57 of 79		XP_016861620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH1	ENST00000420323.7 link	c.8765C>T	p.Ala2922Val	missense_variant	Exon 55 of 78	1	NM_015512.5	ENSP00000401514.2	Q9P2D7-4
DNAH1	ENST00000486752.5 link	n.9026C>T		non_coding_transcript_exon_variant	Exon 55 of 77	2
DNAH1	ENST00000488988.5 link	n.355C>T		non_coding_transcript_exon_variant	Exon 3 of 25	2

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

327

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000785

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00403

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00227

AC:

507

AN:

223620

Hom.:

AF XY:

0.00218

AC XY:

265

AN XY:

121504

show subpopulations

Gnomad AFR exome

AF:

0.000463

Gnomad AMR exome

AF:

0.00141

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00233

Gnomad FIN exome

AF:

0.000796

Gnomad NFE exome

AF:

0.00367

Gnomad OTH exome

AF:

0.00161

GnomAD4 exome

AF:

0.00334

AC:

4846

AN:

1449528

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

2330

AN XY:

720064

show subpopulations

Gnomad4 AFR exome

AF:

0.000602

Gnomad4 AMR exome

AF:

0.00121

Gnomad4 ASJ exome

AF:

0.0000387

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00208

Gnomad4 FIN exome

AF:

0.00109

Gnomad4 NFE exome

AF:

0.00397

Gnomad4 OTH exome

AF:

0.00240

GnomAD4 genome

AF:

0.00214

AC:

326

AN:

152364

Hom.:

Cov.:

AF XY:

0.00183

AC XY:

136

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000409

Gnomad4 AMR

AF:

0.000784

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.00104

Gnomad4 NFE

AF:

0.00401

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00306

Hom.:

Bravo

AF:

0.00190

TwinsUK

AF:

0.00431

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.000233

AC:

ESP6500EA

AF:

0.00402

AC:

ExAC

AF:

0.00215

AC:

260

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

Benign:1

Jan 20, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

DNAH1-related disorder

Benign:1

Feb 03, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.086

Eigen_PC

Benign

0.0056

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.045

MetaRNN

Benign

0.015

MetaSVM

Uncertain

-0.13

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-3.3

REVEL

Uncertain

0.38

Sift

Benign

0.049

Sift4G

Benign

0.090

Vest4

0.63

MVP

0.61

MPC

0.16

ClinPred

0.051

GERP RS

3.6

gMVP

0.55

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