rs149787191

Positions:

• chr6-38894841-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001206927.2(DNAH8):​c.8724G>A​(p.Glu2908=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000559 in 1,613,856 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0024 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00036 (2 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0960

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-38894841-G-A is Benign according to our data. Variant chr6-38894841-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 454605.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.096 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00244 (371/152324) while in subpopulation AFR AF= 0.00804 (334/41566). AF 95% confidence interval is 0.00733. There are 1 homozygotes in gnomad4. There are 164 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.8724G>A	p.Glu2908=	synonymous_variant	59/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.8724G>A	p.Glu2908=	synonymous_variant	59/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.8073G>A	p.Glu2691=	synonymous_variant	57/91	2		A2
DNAH8	ENST00000449981.6	c.8724G>A	p.Glu2908=	synonymous_variant	58/82	5

Frequencies

GnomAD3 genomes AF: 0.00243 AC: 370 AN: 152206 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00803

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00144

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: 0.000132

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.000758 AC: 190 AN: 250716 Hom.: 1 AF XY: 0.000561 AC XY: 76 AN XY: 135502

Gnomad AFR exome AF: 0.00838

Gnomad AMR exome AF: 0.00113

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: 0.000115

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000363 AC: 531 AN: 1461532 Hom.: 2 Cov.: 31 AF XY: 0.000326 AC XY: 237 AN XY: 727044

Gnomad4 AFR exome AF: 0.00801

Gnomad4 AMR exome AF: 0.00128

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000136

Gnomad4 OTH exome AF: 0.000778

GnomAD4 genome AF: 0.00244 AC: 371 AN: 152324 Hom.: 1 Cov.: 32 AF XY: 0.00220 AC XY: 164 AN XY: 74488

Gnomad4 AFR AF: 0.00804

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00142 Hom.: 0

Bravo AF: 0.00277

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign/Likely 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 20, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2022

DNAH8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	2.1
DANN	Benign	0.55

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: rs149787191; hg19: chr6-38862617;