rs9470924

Variant names:

• chr6-38737906-C-T
• rs9470924
• NM_001206927.2:c.1050C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001206927.2(DNAH8):​c.1050C>T​(p.Ala350Ala) 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
• Publications: 6 publications found

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]

DNAH8 Gene-Disease associations (from GenCC):

• spermatogenic failure 46

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• spermatogenic failure 5

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.1050C>T	p.Ala350Ala	synonymous_variant	Exon 7 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.1050C>T	p.Ala350Ala	synonymous_variant	Exon 7 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.399C>T	p.Ala133Ala	synonymous_variant	Exon 5 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.1050C>T	p.Ala350Ala	synonymous_variant	Exon 6 of 82	5		ENSP00000415331.2

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

GnomAD2 exomes AF: 0.0281 AC: 6820 AN: 242306 AF XY: 0.0315

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 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

African (AFR) AF: 0.00287 AC: 94 AN: 32698

American (AMR) AF: 0.0181 AC: 779 AN: 43026

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 305 AN: 25952

East Asian (EAS) AF: 0.0432 AC: 1665 AN: 38568

South Asian (SAS) AF: 0.101 AC: 8639 AN: 85340

European-Finnish (FIN) AF: 0.0159 AC: 850 AN: 53294

Middle Eastern (MID) AF: 0.0269 AC: 155 AN: 5754

European-Non Finnish (NFE) AF: 0.0133 AC: 14748 AN: 1108664

Other (OTH) AF: 0.0218 AC: 1306 AN: 59956

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

African (AFR) AF: 0.00354 AC: 147 AN: 41542

American (AMR) AF: 0.0111 AC: 169 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 39 AN: 3470

East Asian (EAS) AF: 0.0530 AC: 275 AN: 5186

South Asian (SAS) AF: 0.104 AC: 500 AN: 4822

European-Finnish (FIN) AF: 0.0176 AC: 186 AN: 10566

Middle Eastern (MID) AF: 0.0171 AC: 5 AN: 292

European-Non Finnish (NFE) AF: 0.0130 AC: 883 AN: 68008

Other (OTH) AF: 0.0109 AC: 23 AN: 2112

Alfa AF: 0.0126 Hom.: 18

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 04, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	0.67
DANN	Benign	0.43
PhyloP100		-1.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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