rs6935293

chr6-38737167-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):c.863A>G(p.Asn288Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0421 in 1,582,706 control chromosomes in the GnomAD database, including 1,721 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.045 (176 hom., cov: 32)
  • Exomes 𝑓: 0.042 (1545 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.66

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0023658872).
• BP6: Variant 6-38737167-A-G is Benign according to our data. Variant chr6-38737167-A-G is described in ClinVar as [Benign]. Clinvar id is 414419.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.863A>G	p.Asn288Ser	missense_variant	6/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.863A>G	p.Asn288Ser	missense_variant	6/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.212A>G	p.Asn71Ser	missense_variant	4/91	2		A2
DNAH8	ENST00000449981.6	c.863A>G	p.Asn288Ser	missense_variant	5/82	5

Frequencies

GnomAD3 genomes AF: 0.0453 AC: 6897 AN: 152180 Hom.: 175 Cov.: 32

Gnomad AFR AF: 0.0378

Gnomad AMI AF: 0.0702

Gnomad AMR AF: 0.0416

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0956

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0759

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0413

Gnomad OTH AF: 0.0521

GnomAD3 exomes AF: 0.0425 AC: 9749 AN: 229310 Hom.: 217 AF XY: 0.0421 AC XY: 5252 AN XY: 124840

Gnomad AFR exome AF: 0.0326

Gnomad AMR exome AF: 0.0317

Gnomad ASJ exome AF: 0.0391

Gnomad EAS exome AF: 0.0641

Gnomad SAS exome AF: 0.0382

Gnomad FIN exome AF: 0.0739

Gnomad NFE exome AF: 0.0386

Gnomad OTH exome AF: 0.0437

GnomAD4 exome AF: 0.0417 AC: 59659 AN: 1430408 Hom.: 1545 Cov.: 30 AF XY: 0.0417 AC XY: 29628 AN XY: 711010

Gnomad4 AFR exome AF: 0.0369

Gnomad4 AMR exome AF: 0.0344

Gnomad4 ASJ exome AF: 0.0419

Gnomad4 EAS exome AF: 0.117

Gnomad4 SAS exome AF: 0.0402

Gnomad4 FIN exome AF: 0.0724

Gnomad4 NFE exome AF: 0.0379

Gnomad4 OTH exome AF: 0.0430

GnomAD4 genome AF: 0.0453 AC: 6898 AN: 152298 Hom.: 176 Cov.: 32 AF XY: 0.0468 AC XY: 3488 AN XY: 74452

Gnomad4 AFR AF: 0.0378

Gnomad4 AMR AF: 0.0415

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0960

Gnomad4 SAS AF: 0.0472

Gnomad4 FIN AF: 0.0759

Gnomad4 NFE AF: 0.0413

Gnomad4 OTH AF: 0.0543

Alfa AF: 0.0431 Hom.: 163

Bravo AF: 0.0425

TwinsUK AF: 0.0375 AC: 139

ALSPAC AF: 0.0345 AC: 133

ESP6500AA AF: 0.0343 AC: 151

ESP6500EA AF: 0.0407 AC: 350

ExAC AF: 0.0486 AC: 5907

Asia WGS AF: 0.0790 AC: 273 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 04, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.72
Cadd	Benign	14
Dann	Benign	0.79
DEOGEN2	Benign	0.020	T;T;T
Eigen	Benign	-0.70
Eigen_PC	Benign	-0.55
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.74	T;T;T
MetaRNN	Benign	0.0024	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.98	D;D;D
PrimateAI	Benign	0.37	T
REVEL	Benign	0.12
Polyphen		0.011	.;.;B
Vest4		0.056
MPC		0.11
ClinPred		0.0037	T
GERP RS		2.8
Varity_R		0.070
gMVP		0.47

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: rs6935293; hg19: chr6-38704943; COSMIC: COSV59448622; COSMIC: COSV59448622;