rs2050180

Positions:

• chr6-38919777-G-A
• chr6-38919777-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001206927.2(DNAH8):​c.10525-1592G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0712 in 152,040 control chromosomes in the GnomAD database, including 971 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 0.071 (971 hom., cov: 32)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0650

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-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.10525-1592G>A		intron_variant		ENST00000327475.11	NP_001193856.1
DNAH8-AS1	NR_038401.1	n.782+3308C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.10525-1592G>A		intron_variant		5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7	c.9874-1592G>A		intron_variant		2		ENSP00000352312	A2
DNAH8	ENST00000449981.6	c.10525-1592G>A		intron_variant		5		ENSP00000415331

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10819 AN: 151922 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0439

Gnomad ASJ AF: 0.0539

Gnomad EAS AF: 0.151

Gnomad SAS AF: 0.0919

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.00498

Gnomad OTH AF: 0.0629

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

GnomAD4 genome AF: 0.0712 AC: 10829 AN: 152040 Hom.: 971 Cov.: 32 AF XY: 0.0712 AC XY: 5291 AN XY: 74310

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.0438

Gnomad4 ASJ AF: 0.0539

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.0911

Gnomad4 FIN AF: 0.000378

Gnomad4 NFE AF: 0.00499

Gnomad4 OTH AF: 0.0623

Alfa AF: 0.0373 Hom.: 107

Bravo AF: 0.0807

Asia WGS AF: 0.108 AC: 374 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.61

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: rs2050180; hg19: chr6-38887553; COSMIC: COSV59425418; COSMIC: COSV59425418;