rs45529837

chr6-38789839-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001206927.2(DNAH8):c.2620G>A(p.Val874Met) variant causes a missense change. The variant allele was found at a frequency of 0.0289 in 1,612,376 control chromosomes in the GnomAD database, including 791 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (67 hom., cov: 33)
  • Exomes 𝑓: 0.029 (724 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.58

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.003100425).
• BP6: Variant 6-38789839-G-A is Benign according to our data. Variant chr6-38789839-G-A is described in ClinVar as [Benign]. Clinvar id is 414389.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr6-38789839-G-A is described in Lovd as [Benign].
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.061 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.2620G>A	p.Val874Met	missense_variant	19/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.2620G>A	p.Val874Met	missense_variant	19/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.1969G>A	p.Val657Met	missense_variant	17/91	2		A2
DNAH8	ENST00000449981.6	c.2620G>A	p.Val874Met	missense_variant	18/82	5

Frequencies

GnomAD3 genomes AF: 0.0261 AC: 3967 AN: 152154 Hom.: 68 Cov.: 33

Gnomad AFR AF: 0.0143

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0337

Gnomad EAS AF: 0.000961

Gnomad SAS AF: 0.0141

Gnomad FIN AF: 0.0219

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0307

Gnomad OTH AF: 0.0516

GnomAD3 exomes AF: 0.0249 AC: 6238 AN: 250822 Hom.: 112 AF XY: 0.0256 AC XY: 3475 AN XY: 135624

Gnomad AFR exome AF: 0.0131

Gnomad AMR exome AF: 0.0282

Gnomad ASJ exome AF: 0.0310

Gnomad EAS exome AF: 0.000218

Gnomad SAS exome AF: 0.0166

Gnomad FIN exome AF: 0.0222

Gnomad NFE exome AF: 0.0311

Gnomad OTH exome AF: 0.0351

GnomAD4 exome AF: 0.0292 AC: 42676 AN: 1460104 Hom.: 724 Cov.: 30 AF XY: 0.0290 AC XY: 21089 AN XY: 726444

Gnomad4 AFR exome AF: 0.0127

Gnomad4 AMR exome AF: 0.0308

Gnomad4 ASJ exome AF: 0.0324

Gnomad4 EAS exome AF: 0.0000757

Gnomad4 SAS exome AF: 0.0166

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.0318

Gnomad4 OTH exome AF: 0.0293

GnomAD4 genome AF: 0.0260 AC: 3958 AN: 152272 Hom.: 67 Cov.: 33 AF XY: 0.0259 AC XY: 1926 AN XY: 74458

Gnomad4 AFR AF: 0.0142

Gnomad4 AMR AF: 0.0436

Gnomad4 ASJ AF: 0.0337

Gnomad4 EAS AF: 0.000963

Gnomad4 SAS AF: 0.0139

Gnomad4 FIN AF: 0.0219

Gnomad4 NFE AF: 0.0307

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0302 Hom.: 115

Bravo AF: 0.0284

TwinsUK AF: 0.0302 AC: 112

ALSPAC AF: 0.0257 AC: 99

ESP6500AA AF: 0.0168 AC: 74

ESP6500EA AF: 0.0343 AC: 295

ExAC AF: 0.0250 AC: 3034

Asia WGS AF: 0.00664 AC: 23 AN: 3478

EpiCase AF: 0.0327

EpiControl AF: 0.0362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.29
Cadd	Benign	22
Dann	Uncertain	0.99
DEOGEN2	Benign	0.028	T;T;T
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.84	T;T;T
MetaRNN	Benign	0.0031	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.86	D;D;D
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.085
Polyphen		0.12	.;.;B
Vest4		0.23
MPC		0.47
ClinPred		0.011	T
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.10
gMVP		0.26

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

Other links and lift over

dbSNP: rs45529837; hg19: chr6-38757615;