6-38825775-C-G

Variant names:

• chr6-38825775-C-G
• rs1678719
• NM_001206927.2:c.3848-381C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206927.2(DNAH8):​c.3848-381C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.211 in 151,962 control chromosomes in the GnomAD database, including 4,240 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (4240 hom., cov: 32)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0520
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.3848-381C>G		intron_variant	Intron 28 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.3848-381C>G		intron_variant	Intron 28 of 92	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.3197-381C>G		intron_variant	Intron 26 of 90	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.3848-381C>G		intron_variant	Intron 27 of 81	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.211 AC: 31968 AN: 151844 Hom.: 4225 Cov.: 32

Gnomad AFR AF: 0.367

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.181

Gnomad ASJ AF: 0.0976

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.175

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.199

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.211 AC: 32014 AN: 151962 Hom.: 4240 Cov.: 32 AF XY: 0.209 AC XY: 15546 AN XY: 74286

African (AFR) AF: 0.367 AC: 15189 AN: 41392

American (AMR) AF: 0.182 AC: 2774 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0976 AC: 339 AN: 3472

East Asian (EAS) AF: 0.275 AC: 1421 AN: 5164

South Asian (SAS) AF: 0.174 AC: 838 AN: 4812

European-Finnish (FIN) AF: 0.143 AC: 1514 AN: 10562

Middle Eastern (MID) AF: 0.178 AC: 52 AN: 292

European-Non Finnish (NFE) AF: 0.136 AC: 9258 AN: 67980

Other (OTH) AF: 0.198 AC: 417 AN: 2110

Alfa AF: 0.0792 Hom.: 90

Bravo AF: 0.225

Asia WGS AF: 0.223 AC: 773 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	5.7
DANN	Benign	0.33
PhyloP100		-0.052
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: rs1678719; hg19: chr6-38793551;