rs79760452

chr3-52372379-G-A

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_015512.5(DNAH1):c.6819G>A(p.Leu2273=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00486 in 1,613,736 control chromosomes in the GnomAD database, including 607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0042 (43 hom., cov: 33)
  • Exomes 𝑓: 0.0049 (564 hom.)
• Consequence: DNAH1 NM_015512.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.13

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]

ACMG classification

Verdict is Benign. Variant got -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.43).
• BP6: Variant 3-52372379-G-A is Benign according to our data. Variant chr3-52372379-G-A is described in ClinVar as [Benign]. Clinvar id is 478482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH1	NM_015512.5	c.6819G>A	p.Leu2273=	synonymous_variant	43/78	ENST00000420323.7
DNAH1	XM_017006129.2	c.6888G>A	p.Leu2296=	synonymous_variant	45/80
DNAH1	XM_017006130.2	c.6819G>A	p.Leu2273=	synonymous_variant	44/79
DNAH1	XM_017006131.2	c.6888G>A	p.Leu2296=	synonymous_variant	45/79

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH1	ENST00000420323.7	c.6819G>A	p.Leu2273=	synonymous_variant	43/78	1	NM_015512.5	P1
DNAH1	ENST00000486752.5	n.7080G>A		non_coding_transcript_exon_variant	43/77	2

Frequencies

GnomAD3 genomes AF: 0.00421 AC: 640 AN: 152158 Hom.: 43 Cov.: 33

Gnomad AFR AF: 0.0000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.000942

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000191

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00919 AC: 2288 AN: 248850 Hom.: 129 AF XY: 0.00892 AC XY: 1204 AN XY: 135052

Gnomad AFR exome AF: 0.0000646

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.116

Gnomad SAS exome AF: 0.00190

Gnomad FIN exome AF: 0.00136

Gnomad NFE exome AF: 0.000664

Gnomad OTH exome AF: 0.00464

GnomAD4 exome AF: 0.00492 AC: 7195 AN: 1461460 Hom.: 564 Cov.: 32 AF XY: 0.00486 AC XY: 3536 AN XY: 727022

Gnomad4 AFR exome AF: 0.0000299

Gnomad4 AMR exome AF: 0.000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.162

Gnomad4 SAS exome AF: 0.00195

Gnomad4 FIN exome AF: 0.00128

Gnomad4 NFE exome AF: 0.000228

Gnomad4 OTH exome AF: 0.00454

GnomAD4 genome AF: 0.00421 AC: 641 AN: 152276 Hom.: 43 Cov.: 33 AF XY: 0.00477 AC XY: 355 AN XY: 74452

Gnomad4 AFR AF: 0.0000722

Gnomad4 AMR AF: 0.000719

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.000942

Gnomad4 NFE AF: 0.000191

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000589 Hom.: 2

Bravo AF: 0.00437

Asia WGS AF: 0.0390 AC: 135 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000533

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 09, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.43
Cadd	Benign	6.4
Dann	Benign	0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

Other links and lift over

dbSNP: rs79760452; hg19: chr3-52406395; COSMIC: COSV70230153; COSMIC: COSV70230153;