rs1678744

Variant names:

• chr6-38848798-T-C
• rs1678744
• NM_001206927.2:c.5196T>C

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.5196T>C​(p.Pro1732Pro) 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
• Publications: 4 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=-0.61).
• BP6: Variant 6-38848798-T-C is Benign according to our data. Variant chr6-38848798-T-C is described in ClinVar as Benign. ClinVar VariationId is 414401.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. 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.5196T>C	p.Pro1732Pro	synonymous	Exon 37 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.4545T>C	p.Pro1515Pro	synonymous	Exon 36 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.5196T>C	p.Pro1732Pro	synonymous	Exon 37 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.4545T>C	p.Pro1515Pro	synonymous	Exon 35 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.5196T>C	p.Pro1732Pro	synonymous	Exon 36 of 82	ENSP00000415331.2

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

GnomAD2 exomes AF: 0.0305 AC: 7645 AN: 250764 AF XY: 0.0233

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 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

African (AFR) AF: 0.368 AC: 12290 AN: 33402

American (AMR) AF: 0.0284 AC: 1269 AN: 44662

Ashkenazi Jewish (ASJ) AF: 0.0281 AC: 734 AN: 26098

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39674

South Asian (SAS) AF: 0.00312 AC: 269 AN: 86180

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53404

Middle Eastern (MID) AF: 0.0476 AC: 274 AN: 5752

European-Non Finnish (NFE) AF: 0.00283 AC: 3147 AN: 1111328

Other (OTH) AF: 0.0285 AC: 1719 AN: 60330

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

African (AFR) AF: 0.346 AC: 14334 AN: 41418

American (AMR) AF: 0.0511 AC: 781 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0285 AC: 99 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4824

European-Finnish (FIN) AF: 0.000188 AC: 2 AN: 10612

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00393 AC: 267 AN: 68004

Other (OTH) AF: 0.0898 AC: 189 AN: 2104

Alfa AF: 0.0419 Hom.: 1528

Bravo AF: 0.122

Asia WGS AF: 0.0240 AC: 84 AN: 3478

EpiCase AF: 0.00404

EpiControl AF: 0.00462

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.8
DANN	Benign	0.81
PhyloP100		-0.63
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: rs1678744; hg19: chr6-38816574;