6-38931709-G-C

Position:

• chr6-38931709-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001206927.2(DNAH8):​c.11275-102G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 602,622 control chromosomes in the GnomAD database, including 152,225 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.74 (42475 hom., cov: 32)
  • Exomes 𝑓: 0.69 (109750 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.990

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-38931709-G-C is Benign according to our data. Variant chr6-38931709-G-C is described in ClinVar as [Benign]. Clinvar id is 1295609.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.855 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.11275-102G>C		intron_variant		ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.160+4584C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.11275-102G>C		intron_variant		5	NM_001206927.2	P2
DNAH8-AS1	ENST00000416948.1	n.152+4584C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112645 AN: 151954 Hom.: 42407 Cov.: 32

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.649

Gnomad AMR AF: 0.768

Gnomad ASJ AF: 0.605

Gnomad EAS AF: 0.860

Gnomad SAS AF: 0.693

Gnomad FIN AF: 0.670

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.677

Gnomad OTH AF: 0.693

GnomAD4 exome AF: 0.694 AC: 312717 AN: 450550 Hom.: 109750 AF XY: 0.691 AC XY: 161252 AN XY: 233358

Gnomad4 AFR exome AF: 0.868

Gnomad4 AMR exome AF: 0.789

Gnomad4 ASJ exome AF: 0.615

Gnomad4 EAS exome AF: 0.816

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.668

Gnomad4 NFE exome AF: 0.680

Gnomad4 OTH exome AF: 0.696

GnomAD4 genome AF: 0.742 AC: 112772 AN: 152072 Hom.: 42475 Cov.: 32 AF XY: 0.741 AC XY: 55057 AN XY: 74340

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.768

Gnomad4 ASJ AF: 0.605

Gnomad4 EAS AF: 0.860

Gnomad4 SAS AF: 0.693

Gnomad4 FIN AF: 0.670

Gnomad4 NFE AF: 0.677

Gnomad4 OTH AF: 0.696

Alfa AF: 0.712 Hom.: 4850

Bravo AF: 0.753

Asia WGS AF: 0.780 AC: 2710 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.69
DANN	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs9296268; hg19: chr6-38899485;