rs149534667

chr6-38775873-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001206927.2(DNAH8):c.1884A>G(p.Gln628=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000569 in 1,612,684 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (2 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.704

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 6-38775873-A-G is Benign according to our data. Variant chr6-38775873-A-G is described in ClinVar as [Benign]. Clinvar id is 454559.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.704 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00289 (440/152356) while in subpopulation AFR AF= 0.00984 (409/41586). AF 95% confidence interval is 0.00905. There are 2 homozygotes in gnomad4. There are 210 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.1884A>G	p.Gln628=	synonymous_variant	13/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.1884A>G	p.Gln628=	synonymous_variant	13/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.1233A>G	p.Gln411=	synonymous_variant	11/91	2		A2
DNAH8	ENST00000449981.6	c.1884A>G	p.Gln628=	synonymous_variant	12/82	5

Frequencies

GnomAD3 genomes AF: 0.00289 AC: 440 AN: 152238 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00986

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

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: 0.00143

GnomAD3 exomes AF: 0.000761 AC: 191 AN: 250838 Hom.: 0 AF XY: 0.000685 AC XY: 93 AN XY: 135728

Gnomad AFR exome AF: 0.00955

Gnomad AMR exome AF: 0.000695

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: 0.000164

GnomAD4 exome AF: 0.000327 AC: 477 AN: 1460328 Hom.: 2 Cov.: 29 AF XY: 0.000329 AC XY: 239 AN XY: 726622

Gnomad4 AFR exome AF: 0.00981

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000232

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000702

Gnomad4 OTH exome AF: 0.000663

GnomAD4 genome AF: 0.00289 AC: 440 AN: 152356 Hom.: 2 Cov.: 32 AF XY: 0.00282 AC XY: 210 AN XY: 74500

Gnomad4 AFR AF: 0.00984

Gnomad4 AMR AF: 0.00124

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: 0.00142

Alfa AF: 0.00171 Hom.: 1

Bravo AF: 0.00351

Asia WGS AF: 0.000578 AC: 2 AN: 3476

EpiCase AF: 0.000218

EpiControl AF: 0.000178

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 20, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.47
Dann	Benign	0.40

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: rs149534667; hg19: chr6-38743649;