rs9394550

Positions:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.8259+1187G>A		intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.8259+1187G>A		intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.7608+1187G>A		intron_variant		2		A2
DNAH8	ENST00000449981.6	c.8259+1187G>A		intron_variant		5

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

Gnomad4 AFR AF: 0.410

Gnomad4 AMR AF: 0.537

Gnomad4 ASJ AF: 0.360

Gnomad4 EAS AF: 0.842

Gnomad4 SAS AF: 0.556

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.440

Alfa AF: 0.437 Hom.: 7405

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs9394550; hg19: chr6-38852961;