rs117061525

Positions:

• chr6-38786918-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.2549A>G​(p.Glu850Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000818 in 1,610,202 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00083 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00082 (16 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.99

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=0.006804198).
• BP6: Variant 6-38786918-A-G is Benign according to our data. Variant chr6-38786918-A-G is described in ClinVar as [Benign]. Clinvar id is 238639.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000834 (127/152286) while in subpopulation EAS AF= 0.0228 (118/5184). AF 95% confidence interval is 0.0194. There are 1 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.2549A>G	p.Glu850Gly	missense_variant	18/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.2549A>G	p.Glu850Gly	missense_variant	18/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.1898A>G	p.Glu633Gly	missense_variant	16/91	2		A2
DNAH8	ENST00000449981.6	c.2549A>G	p.Glu850Gly	missense_variant	17/82	5

Frequencies

GnomAD3 genomes AF: 0.000841 AC: 128 AN: 152168 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0227

Gnomad SAS AF: 0.00187

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00187 AC: 464 AN: 248460 Hom.: 2 AF XY: 0.00171 AC XY: 230 AN XY: 134276

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000592

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0236

Gnomad SAS exome AF: 0.000936

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000887

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000816 AC: 1190 AN: 1457916 Hom.: 16 Cov.: 30 AF XY: 0.000840 AC XY: 609 AN XY: 724914

Gnomad4 AFR exome AF: 0.0000300

Gnomad4 AMR exome AF: 0.0000681

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0262

Gnomad4 SAS exome AF: 0.000914

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.000813

GnomAD4 genome AF: 0.000834 AC: 127 AN: 152286 Hom.: 1 Cov.: 33 AF XY: 0.000953 AC XY: 71 AN XY: 74470

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.0000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0228

Gnomad4 SAS AF: 0.00166

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00149 Hom.: 4

Bravo AF: 0.00114

ExAC AF: 0.00181 AC: 220

Asia WGS AF: 0.00491 AC: 18 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

Jan 27, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.55
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.069	T;T;T
Eigen	Benign	0.12
Eigen_PC	Uncertain	0.25
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.73	T;T;T
MetaRNN	Benign	0.0068	T;T;T
MetaSVM	Benign	-0.92	T
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.51	T
REVEL	Benign	0.28
Polyphen		0.014	.;.;B
Vest4		0.65
MVP		0.65
MPC		0.20
ClinPred		0.078	T
GERP RS		5.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.45
gMVP		0.54

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: rs117061525; hg19: chr6-38754694; COSMIC: COSV59433320;