6-38722581-G-T

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.-34-195G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 150,772 control chromosomes in the GnomAD database, including 7,024 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.30 (7024 hom., cov: 29)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.20

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=-0.89).
• BP6: Variant 6-38722581-G-T is Benign according to our data. Variant chr6-38722581-G-T is described in ClinVar as [Benign]. Clinvar id is 1240529.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.344 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.-34-195G>T		intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.-34-195G>T		intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000373278.8	c.-34-195G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45279 AN: 150660 Hom.: 7010 Cov.: 29

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.353

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.327

Gnomad MID AF: 0.223

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.301 AC: 45328 AN: 150772 Hom.: 7024 Cov.: 29 AF XY: 0.299 AC XY: 21986 AN XY: 73586

Gnomad4 AFR AF: 0.317

Gnomad4 AMR AF: 0.352

Gnomad4 ASJ AF: 0.353

Gnomad4 EAS AF: 0.0614

Gnomad4 SAS AF: 0.130

Gnomad4 FIN AF: 0.327

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.295

Alfa AF: 0.279 Hom.: 360

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.11
Dann	Benign	0.67

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: rs111396453; hg19: chr6-38690357; COSMIC: COSV59461451; COSMIC: COSV59461451;