6-38852768-C-T

Variant names:

• chr6-38852768-C-T
• rs1678746
• NM_001206927.2:c.5541C>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.5541C>T​(p.Ala1847Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.021 in 1,612,566 control chromosomes in the GnomAD database, including 4,578 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.099 (2311 hom., cov: 32)
  • Exomes 𝑓: 0.013 (2267 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.928
• Publications: 3 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=-0.59).
• BP6: Variant 6-38852768-C-T is Benign according to our data. Variant chr6-38852768-C-T is described in ClinVar as Benign. ClinVar VariationId is 414409.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.928 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.5541C>T	p.Ala1847Ala	synonymous_variant	Exon 40 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.5541C>T	p.Ala1847Ala	synonymous_variant	Exon 40 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.4890C>T	p.Ala1630Ala	synonymous_variant	Exon 38 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.5541C>T	p.Ala1847Ala	synonymous_variant	Exon 39 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14954 AN: 151824 Hom.: 2302 Cov.: 32

Gnomad AFR AF: 0.330

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0497

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000190

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.00393

Gnomad OTH AF: 0.0872

GnomAD2 exomes AF: 0.0288 AC: 7218 AN: 250716 AF XY: 0.0219

Gnomad AFR exome AF: 0.344

Gnomad AMR exome AF: 0.0233

Gnomad ASJ exome AF: 0.0273

Gnomad EAS exome AF: 0.0000545

Gnomad FIN exome AF: 0.000139

Gnomad NFE exome AF: 0.00345

Gnomad OTH exome AF: 0.0177

GnomAD4 exome AF: 0.0129 AC: 18846 AN: 1460624 Hom.: 2267 Cov.: 31 AF XY: 0.0116 AC XY: 8445 AN XY: 726646

African (AFR) AF: 0.349 AC: 11623 AN: 33294

American (AMR) AF: 0.0270 AC: 1208 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.0278 AC: 726 AN: 26096

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39674

South Asian (SAS) AF: 0.00297 AC: 256 AN: 86102

European-Finnish (FIN) AF: 0.000131 AC: 7 AN: 53364

Middle Eastern (MID) AF: 0.0453 AC: 261 AN: 5756

European-Non Finnish (NFE) AF: 0.00281 AC: 3121 AN: 1111334

Other (OTH) AF: 0.0272 AC: 1642 AN: 60338

GnomAD4 genome AF: 0.0987 AC: 14992 AN: 151942 Hom.: 2311 Cov.: 32 AF XY: 0.0955 AC XY: 7096 AN XY: 74266

African (AFR) AF: 0.330 AC: 13660 AN: 41390

American (AMR) AF: 0.0496 AC: 756 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0289 AC: 100 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00208 AC: 10 AN: 4816

European-Finnish (FIN) AF: 0.000190 AC: 2 AN: 10546

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00393 AC: 267 AN: 67988

Other (OTH) AF: 0.0863 AC: 182 AN: 2108

Alfa AF: 0.0508 Hom.: 829

Bravo AF: 0.117

Asia WGS AF: 0.0210 AC: 74 AN: 3478

EpiCase AF: 0.00366

EpiControl AF: 0.00445

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	-0.59
CADD	Benign	0.64
DANN	Benign	0.51
PhyloP100		-0.93
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1678746; hg19: chr6-38820544;