rs147580001

chr6-38737136-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001206927.2(DNAH8):c.832A>G(p.Ile278Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000472 in 1,587,412 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0026 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (4 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.255

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=0.009552956).
• BP6: Variant 6-38737136-A-G is Benign according to our data. Variant chr6-38737136-A-G is described in ClinVar as [Benign]. Clinvar id is 454601.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00257 (392/152318) while in subpopulation AFR AF= 0.00868 (361/41576). AF 95% confidence interval is 0.00794. There are 3 homozygotes in gnomad4. There are 178 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.832A>G	p.Ile278Val	missense_variant	6/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.832A>G	p.Ile278Val	missense_variant	6/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.181A>G	p.Ile61Val	missense_variant	4/91	2		A2
DNAH8	ENST00000449981.6	c.832A>G	p.Ile278Val	missense_variant	5/82	5

Frequencies

GnomAD3 genomes AF: 0.00258 AC: 393 AN: 152200 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00873

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000982

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000634 AC: 147 AN: 232008 Hom.: 2 AF XY: 0.000349 AC XY: 44 AN XY: 126144

Gnomad AFR exome AF: 0.00896

Gnomad AMR exome AF: 0.000385

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000925

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000249 AC: 357 AN: 1435094 Hom.: 4 Cov.: 30 AF XY: 0.000198 AC XY: 141 AN XY: 713502

Gnomad4 AFR exome AF: 0.00905

Gnomad4 AMR exome AF: 0.000429

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000371

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000818

Gnomad4 OTH exome AF: 0.000607

GnomAD4 genome AF: 0.00257 AC: 392 AN: 152318 Hom.: 3 Cov.: 32 AF XY: 0.00239 AC XY: 178 AN XY: 74470

Gnomad4 AFR AF: 0.00868

Gnomad4 AMR AF: 0.000981

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000147

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000491 Hom.: 2

Bravo AF: 0.00291

ESP6500AA AF: 0.00817 AC: 36

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000766 AC: 93

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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

Dec 25, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.63	T
BayesDel_noAF	Benign	-0.67
Cadd	Benign	4.9
Dann	Benign	0.19
DEOGEN2	Benign	0.0019	T;T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.56	T;T;T
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.0096	T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.31	T
REVEL	Benign	0.027
Polyphen		0.0040	.;.;B
Vest4		0.060
MVP		0.17
MPC		0.10
ClinPred		0.0035	T
GERP RS		-0.20
Varity_R		0.022
gMVP		0.29

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: rs147580001; hg19: chr6-38704912;