6-38919777-G-A

Variant names:

• chr6-38919777-G-A
• rs2050180
• NM_001206927.2:c.10525-1592G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.10525-1592G>A		intron	N/A	NP_001193856.1
	DNAH8	NM_001371.4		c.9874-1592G>A		intron	N/A	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.782+3308C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.10525-1592G>A		intron	N/A	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.9874-1592G>A		intron	N/A	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.10525-1592G>A		intron	N/A	ENSP00000415331.2

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

African (AFR) AF: 0.200 AC: 8263 AN: 41414

American (AMR) AF: 0.0438 AC: 669 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0539 AC: 187 AN: 3468

East Asian (EAS) AF: 0.151 AC: 779 AN: 5168

South Asian (SAS) AF: 0.0911 AC: 439 AN: 4818

European-Finnish (FIN) AF: 0.000378 AC: 4 AN: 10574

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00499 AC: 339 AN: 68000

Other (OTH) AF: 0.0623 AC: 131 AN: 2104

Alfa AF: 0.0676 Hom.: 560

Bravo AF: 0.0807

Asia WGS AF: 0.108 AC: 374 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	3.6
DANN	Benign	0.61
PhyloP100		0.065
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: rs2050180; hg19: chr6-38887553; COSMIC: COSV59425418; COSMIC: COSV59425418;