rs1678744

chr6-38848798-T-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001206927.2(DNAH8):c.5196T>C(p.Pro1732=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.022 in 1,612,938 control chromosomes in the GnomAD database, including 5,072 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (2560 hom., cov: 32)
  • Exomes 𝑓: 0.013 (2512 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.631

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=-0.61).
• BP6: Variant 6-38848798-T-C is Benign according to our data. Variant chr6-38848798-T-C is described in ClinVar as [Benign]. Clinvar id is 414401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr6-38848798-T-C is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=-0.631 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.341 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.5196T>C	p.Pro1732=	synonymous_variant	37/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.5196T>C	p.Pro1732=	synonymous_variant	37/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.4545T>C	p.Pro1515=	synonymous_variant	35/91	2		A2
DNAH8	ENST00000449981.6	c.5196T>C	p.Pro1732=	synonymous_variant	36/82	5

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15656 AN: 151990 Hom.: 2550 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0512

Gnomad ASJ AF: 0.0285

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000188

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00393

Gnomad OTH AF: 0.0908

GnomAD3 exomes AF: 0.0305 AC: 7645 AN: 250764 Hom.: 1105 AF XY: 0.0233 AC XY: 3152 AN XY: 135544

Gnomad AFR exome AF: 0.364

Gnomad AMR exome AF: 0.0245

Gnomad ASJ exome AF: 0.0277

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00282

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00359

Gnomad OTH exome AF: 0.0191

GnomAD4 exome AF: 0.0135 AC: 19711 AN: 1460830 Hom.: 2512 Cov.: 30 AF XY: 0.0122 AC XY: 8831 AN XY: 726722

Gnomad4 AFR exome AF: 0.368

Gnomad4 AMR exome AF: 0.0284

Gnomad4 ASJ exome AF: 0.0281

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00312

Gnomad4 FIN exome AF: 0.000150

Gnomad4 NFE exome AF: 0.00283

Gnomad4 OTH exome AF: 0.0285

GnomAD4 genome AF: 0.103 AC: 15698 AN: 152108 Hom.: 2560 Cov.: 32 AF XY: 0.0998 AC XY: 7426 AN XY: 74372

Gnomad4 AFR AF: 0.346

Gnomad4 AMR AF: 0.0511

Gnomad4 ASJ AF: 0.0285

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000188

Gnomad4 NFE AF: 0.00393

Gnomad4 OTH AF: 0.0898

Alfa AF: 0.0307 Hom.: 796

Bravo AF: 0.122

Asia WGS AF: 0.0240 AC: 84 AN: 3478

EpiCase AF: 0.00404

EpiControl AF: 0.00462

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
BayesDel_noAF	Benign	-0.61
Cadd	Benign	8.8
Dann	Benign	0.81

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: rs1678744; hg19: chr6-38816574;