rs9394550

Variant names:

• chr6-38885185-G-A
• rs9394550
• NM_001206927.2:c.8259+1187G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-38885185-G-A
• chr6-38885185-G-C

Variant summary

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

The NM_001206927.2(DNAH8):​c.8259+1187G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 151,896 control chromosomes in the GnomAD database, including 15,842 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 0.44 (15842 hom., cov: 31)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.197
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.8259+1187G>A		intron_variant	Intron 56 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.8259+1187G>A		intron_variant	Intron 56 of 92	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.7608+1187G>A		intron_variant	Intron 54 of 90	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.8259+1187G>A		intron_variant	Intron 55 of 81	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67464 AN: 151778 Hom.: 15800 Cov.: 31

Gnomad AFR AF: 0.409

Gnomad AMI AF: 0.444

Gnomad AMR AF: 0.536

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.405

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.435

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

GnomAD4 genome AF: 0.445 AC: 67563 AN: 151896 Hom.: 15842 Cov.: 31 AF XY: 0.447 AC XY: 33145 AN XY: 74220

African (AFR) AF: 0.410 AC: 16971 AN: 41396

American (AMR) AF: 0.537 AC: 8206 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1248 AN: 3470

East Asian (EAS) AF: 0.842 AC: 4353 AN: 5170

South Asian (SAS) AF: 0.556 AC: 2668 AN: 4798

European-Finnish (FIN) AF: 0.372 AC: 3928 AN: 10550

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28737 AN: 67930

Other (OTH) AF: 0.440 AC: 925 AN: 2100

Alfa AF: 0.436 Hom.: 8111

Bravo AF: 0.455

Asia WGS AF: 0.680 AC: 2366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.0
DANN	Benign	0.74
PhyloP100		-0.20
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: rs9394550; hg19: chr6-38852961;