6-38884004-G-A

Variant names:

• chr6-38884004-G-A
• rs112605623
• NM_001206927.2:c.8259+6G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001206927.2(DNAH8):​c.8259+6G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0012 in 1,528,264 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0060 (7 hom., cov: 32)
  • Exomes 𝑓: 0.00067 (9 hom.)
• Consequence: DNAH8 NM_001206927.2 splice_region, intron
• Scores: Splicing: ADA: 0.00002157
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.271
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-38884004-G-A is Benign according to our data. Variant chr6-38884004-G-A is described in ClinVar as Benign. ClinVar VariationId is 238656.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00597 (907/151804) while in subpopulation AFR AF = 0.0192 (797/41430). AF 95% confidence interval is 0.0181. There are 7 homozygotes in GnomAd4. There are 426 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.00599 AC: 908 AN: 151690 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.0193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00486

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000339

Gnomad OTH AF: 0.00575

GnomAD2 exomes AF: 0.00149 AC: 331 AN: 221438 AF XY: 0.00112

Gnomad AFR exome AF: 0.0196

Gnomad AMR exome AF: 0.00139

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000117

Gnomad OTH exome AF: 0.00137

GnomAD4 exome AF: 0.000668 AC: 920 AN: 1376460 Hom.: 9 Cov.: 28 AF XY: 0.000625 AC XY: 427 AN XY: 683040

African (AFR) AF: 0.0198 AC: 613 AN: 30938

American (AMR) AF: 0.00189 AC: 74 AN: 39108

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23920

East Asian (EAS) AF: 0.00 AC: 0 AN: 36074

South Asian (SAS) AF: 0.0000422 AC: 3 AN: 71150

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48284

Middle Eastern (MID) AF: 0.00165 AC: 9 AN: 5446

European-Non Finnish (NFE) AF: 0.000128 AC: 136 AN: 1065474

Other (OTH) AF: 0.00152 AC: 85 AN: 56066

GnomAD4 genome AF: 0.00597 AC: 907 AN: 151804 Hom.: 7 Cov.: 32 AF XY: 0.00574 AC XY: 426 AN XY: 74224

African (AFR) AF: 0.0192 AC: 797 AN: 41430

American (AMR) AF: 0.00486 AC: 74 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10454

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000339 AC: 23 AN: 67926

Other (OTH) AF: 0.00569 AC: 12 AN: 2108

Alfa AF: 0.00203 Hom.: 0

Bravo AF: 0.00680

Asia WGS AF: 0.00173 AC: 6 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Jan 28, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.62
DANN	Benign	0.25
PhyloP100		-0.27
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000022
dbscSNV1_RF	Benign	0.0020
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: rs112605623; hg19: chr6-38851780;