6-38931709-G-C

Variant names:

• chr6-38931709-G-C
• rs9296268
• NM_001206927.2:c.11275-102G>C

Variant summary

Our verdict is Benign. The variant received -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
• 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 -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 VariationId 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 rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.11275-102G>C		intron_variant	Intron 75 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.11275-102G>C		intron_variant	Intron 75 of 92	5	NM_001206927.2	ENSP00000333363.7

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

African (AFR) AF: 0.868 AC: 9575 AN: 11030

American (AMR) AF: 0.789 AC: 13260 AN: 16804

Ashkenazi Jewish (ASJ) AF: 0.615 AC: 6890 AN: 11204

East Asian (EAS) AF: 0.816 AC: 22332 AN: 27382

South Asian (SAS) AF: 0.670 AC: 12986 AN: 19386

European-Finnish (FIN) AF: 0.668 AC: 27699 AN: 41474

Middle Eastern (MID) AF: 0.615 AC: 1144 AN: 1860

European-Non Finnish (NFE) AF: 0.680 AC: 202751 AN: 298300

Other (OTH) AF: 0.696 AC: 16080 AN: 23110

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

African (AFR) AF: 0.862 AC: 35807 AN: 41518

American (AMR) AF: 0.768 AC: 11735 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.605 AC: 2094 AN: 3464

East Asian (EAS) AF: 0.860 AC: 4451 AN: 5176

South Asian (SAS) AF: 0.693 AC: 3338 AN: 4820

European-Finnish (FIN) AF: 0.670 AC: 7080 AN: 10560

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.677 AC: 46003 AN: 67950

Other (OTH) AF: 0.696 AC: 1467 AN: 2108

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

Nov 11, 2018

GeneDx

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	-0.90
CADD	Benign	0.69
DANN	Benign	0.50
PhyloP100		-0.99
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9296268; hg19: chr6-38899485;