rs9470924

chr6-38737906-C-T

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.1050C>T(p.Ala350=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 1,605,436 control chromosomes in the GnomAD database, including 755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (43 hom., cov: 32)
  • Exomes 𝑓: 0.020 (712 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.54

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=-0.74).
• BP6: Variant 6-38737906-C-T is Benign according to our data. Variant chr6-38737906-C-T is described in ClinVar as [Benign]. Clinvar id is 414417.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.54 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.1050C>T	p.Ala350=	synonymous_variant	7/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.1050C>T	p.Ala350=	synonymous_variant	7/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.399C>T	p.Ala133=	synonymous_variant	5/91	2		A2
DNAH8	ENST00000449981.6	c.1050C>T	p.Ala350=	synonymous_variant	6/82	5

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2259 AN: 152066 Hom.: 43 Cov.: 32

Gnomad AFR AF: 0.00355

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.0112

Gnomad EAS AF: 0.0535

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0176

Gnomad MID AF: 0.0159

Gnomad NFE AF: 0.0130

Gnomad OTH AF: 0.0110

GnomAD3 exomes AF: 0.0281 AC: 6820 AN: 242306 Hom.: 213 AF XY: 0.0315 AC XY: 4141 AN XY: 131528

Gnomad AFR exome AF: 0.00346

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0131

Gnomad EAS exome AF: 0.0499

Gnomad SAS exome AF: 0.101

Gnomad FIN exome AF: 0.0162

Gnomad NFE exome AF: 0.0154

Gnomad OTH exome AF: 0.0184

GnomAD4 exome AF: 0.0196 AC: 28541 AN: 1453252 Hom.: 712 Cov.: 30 AF XY: 0.0221 AC XY: 15998 AN XY: 723212

Gnomad4 AFR exome AF: 0.00287

Gnomad4 AMR exome AF: 0.0181

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.0432

Gnomad4 SAS exome AF: 0.101

Gnomad4 FIN exome AF: 0.0159

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0218

GnomAD4 genome AF: 0.0148 AC: 2251 AN: 152184 Hom.: 43 Cov.: 32 AF XY: 0.0164 AC XY: 1217 AN XY: 74394

Gnomad4 AFR AF: 0.00354

Gnomad4 AMR AF: 0.0111

Gnomad4 ASJ AF: 0.0112

Gnomad4 EAS AF: 0.0530

Gnomad4 SAS AF: 0.104

Gnomad4 FIN AF: 0.0176

Gnomad4 NFE AF: 0.0130

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0128 Hom.: 16

Bravo AF: 0.0123

Asia WGS AF: 0.0780 AC: 271 AN: 3478

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 29, 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	-0.74
Cadd	Benign	0.67
Dann	Benign	0.43
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9470924; hg19: chr6-38705682; COSMIC: COSV59448652; COSMIC: COSV59448652;