6-38725585-G-A

Variant names:

• chr6-38725585-G-A
• rs7761629
• NM_001206927.2:c.525+2114G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001206927.2(DNAH8):​c.525+2114G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0512 in 152,108 control chromosomes in the GnomAD database, including 226 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 0.051 (226 hom., cov: 31)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.259
• 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 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=-0.89).
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.0512 (7789/152108) while in subpopulation EAS AF = 0.0525 (272/5182). AF 95% confidence interval is 0.0494. There are 226 homozygotes in GnomAd4. There are 3936 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 226 AR gene

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.525+2114G>A		intron	N/A	NP_001193856.1
	DNAH8	NM_001371.4		c.-42+2114G>A		intron	N/A	NP_001362.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.525+2114G>A		intron	N/A	ENSP00000333363.7
	DNAH8	ENST00000373278.8	TSL:1	c.525+2114G>A		intron	N/A	ENSP00000362375.4
	DNAH8	ENST00000359357.7	TSL:2	c.-42+2114G>A		intron	N/A	ENSP00000352312.3

Frequencies

GnomAD3 genomes AF: 0.0513 AC: 7793 AN: 151990 Hom.: 226 Cov.: 31

Gnomad AFR AF: 0.0513

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.0478

Gnomad ASJ AF: 0.0378

Gnomad EAS AF: 0.0522

Gnomad SAS AF: 0.0494

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0469

Gnomad OTH AF: 0.0600

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

GnomAD4 genome AF: 0.0512 AC: 7789 AN: 152108 Hom.: 226 Cov.: 31 AF XY: 0.0529 AC XY: 3936 AN XY: 74356

African (AFR) AF: 0.0512 AC: 2124 AN: 41480

American (AMR) AF: 0.0477 AC: 729 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0378 AC: 131 AN: 3464

East Asian (EAS) AF: 0.0525 AC: 272 AN: 5182

South Asian (SAS) AF: 0.0492 AC: 237 AN: 4818

European-Finnish (FIN) AF: 0.0807 AC: 854 AN: 10576

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0469 AC: 3188 AN: 67992

Other (OTH) AF: 0.0594 AC: 125 AN: 2106

Alfa AF: 0.0476 Hom.: 267

Bravo AF: 0.0488

Asia WGS AF: 0.0510 AC: 177 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.8
DANN	Benign	0.74
PhyloP100		0.26
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: rs7761629; hg19: chr6-38693361;