6-38722587-T-G

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.-34-189T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 149,718 control chromosomes in the GnomAD database, including 9,171 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (9171 hom., cov: 28)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.872

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 6-38722587-T-G is Benign according to our data. Variant chr6-38722587-T-G is described in ClinVar as [Benign]. Clinvar id is 1231898.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.-34-189T>G		intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.-34-189T>G		intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000373278.8	c.-34-189T>G		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 50852 AN: 149602 Hom.: 9156 Cov.: 28

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.293

Gnomad EAS AF: 0.801

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.279

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.331

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

GnomAD4 genome AF: 0.340 AC: 50899 AN: 149718 Hom.: 9171 Cov.: 28 AF XY: 0.342 AC XY: 24976 AN XY: 72996

Gnomad4 AFR AF: 0.337

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.293

Gnomad4 EAS AF: 0.800

Gnomad4 SAS AF: 0.436

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.330

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

May 11, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	6.2
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs34874997; hg19: chr6-38690363;