6-38814090-C-G

Variant names:

• chr6-38814090-C-G
• rs1678690
• NM_001206927.2:c.3294C>G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The ENST00000327475.11(DNAH8):​c.3294C>G​(p.Ser1098Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,572,462 control chromosomes in the GnomAD database, including 158,027 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. S1098S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.42 (14259 hom., cov: 32)
  • Exomes 𝑓: 0.44 (143768 hom.)
• Consequence: DNAH8 ENST00000327475.11 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0570
• Publications: 10 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 6-38814090-C-G is Benign according to our data. Variant chr6-38814090-C-G is described in ClinVar as Benign. ClinVar VariationId is 402763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.057 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.774 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000327475.11. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.3294C>G	p.Ser1098Ser	synonymous	Exon 25 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.2643C>G	p.Ser881Ser	synonymous	Exon 24 of 92	NP_001362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.3294C>G	p.Ser1098Ser	synonymous	Exon 25 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.2643C>G	p.Ser881Ser	synonymous	Exon 23 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.3294C>G	p.Ser1098Ser	synonymous	Exon 24 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.418 AC: 63500 AN: 151852 Hom.: 14225 Cov.: 32

Gnomad AFR AF: 0.331

Gnomad AMI AF: 0.468

Gnomad AMR AF: 0.513

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.794

Gnomad SAS AF: 0.520

Gnomad FIN AF: 0.364

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.390

GnomAD2 exomes AF: 0.476 AC: 118182 AN: 248150 AF XY: 0.468

Gnomad AFR exome AF: 0.328

Gnomad AMR exome AF: 0.646

Gnomad ASJ exome AF: 0.379

Gnomad EAS exome AF: 0.801

Gnomad FIN exome AF: 0.365

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.418

GnomAD4 exome AF: 0.441 AC: 626044 AN: 1420492 Hom.: 143768 Cov.: 29 AF XY: 0.441 AC XY: 312483 AN XY: 708640

African (AFR) AF: 0.322 AC: 10547 AN: 32710

American (AMR) AF: 0.631 AC: 27640 AN: 43778

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 9829 AN: 25886

East Asian (EAS) AF: 0.783 AC: 30719 AN: 39248

South Asian (SAS) AF: 0.493 AC: 41646 AN: 84398

European-Finnish (FIN) AF: 0.369 AC: 19690 AN: 53352

Middle Eastern (MID) AF: 0.359 AC: 2043 AN: 5696

European-Non Finnish (NFE) AF: 0.425 AC: 457931 AN: 1076538

Other (OTH) AF: 0.442 AC: 25999 AN: 58886

GnomAD4 genome AF: 0.418 AC: 63576 AN: 151970 Hom.: 14259 Cov.: 32 AF XY: 0.420 AC XY: 31198 AN XY: 74262

African (AFR) AF: 0.331 AC: 13720 AN: 41452

American (AMR) AF: 0.514 AC: 7851 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1317 AN: 3470

East Asian (EAS) AF: 0.795 AC: 4099 AN: 5158

South Asian (SAS) AF: 0.519 AC: 2501 AN: 4822

European-Finnish (FIN) AF: 0.364 AC: 3834 AN: 10526

Middle Eastern (MID) AF: 0.398 AC: 117 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28874 AN: 67952

Other (OTH) AF: 0.396 AC: 838 AN: 2116

Alfa AF: 0.332 Hom.: 1463

Bravo AF: 0.428

EpiCase AF: 0.421

EpiControl AF: 0.410

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	not specified (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	6.9
DANN	Benign	0.73
PhyloP100		0.057
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	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: rs1678690; hg19: chr6-38781866; COSMIC: COSV59445625;