Variant rs111791517 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_001206927.2(DNAH8):c.11361A>G(p.Pro3787=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,612,086 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.013 ( 35 hom., cov: 31)

Exomes 𝑓: 0.0029 ( 54 hom. )

Consequence

DNAH8
NM_001206927.2 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.244

Variant links:

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 links:

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

DNAH8-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 6-38931897-A-G is Benign according to our data. Variant chr6-38931897-A-G is described in ClinVar as [Benign]. Clinvar id is 414421.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.244 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0128 (1946/152194) while in subpopulation AFR AF= 0.0369 (1532/41518). AF 95% confidence interval is 0.0354. There are 35 homozygotes in gnomad4. There are 939 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.11361A>G	p.Pro3787=	synonymous_variant	76/93	ENST00000327475.11
DNAH8-AS1	NR_038401.1 linkuse as main transcript	n.160+4396T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.11361A>G	p.Pro3787=	synonymous_variant	76/93	5	NM_001206927.2	P2
DNAH8-AS1	ENST00000416948.1 linkuse as main transcript	n.152+4396T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0128

AC:

1940

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0368

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0125

Gnomad ASJ

AF:

0.0153

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.00194

Gnomad OTH

AF:

0.0124

GnomAD3 exomes

AF:

0.00504

AC:

1256

AN:

249126

Hom.:

AF XY:

0.00414

AC XY:

558

AN XY:

134630

show subpopulations

Gnomad AFR exome

AF:

0.0351

Gnomad AMR exome

AF:

0.00813

Gnomad ASJ exome

AF:

0.0175

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000264

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00175

Gnomad OTH exome

AF:

0.00496

GnomAD4 exome

AF:

0.00289

AC:

4213

AN:

1459892

Hom.:

Cov.:

AF XY:

0.00269

AC XY:

1955

AN XY:

726256

show subpopulations

Gnomad4 AFR exome

AF:

0.0389

Gnomad4 AMR exome

AF:

0.00812

Gnomad4 ASJ exome

AF:

0.0166

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000291

Gnomad4 FIN exome

AF:

0.0000936

Gnomad4 NFE exome

AF:

0.00143

Gnomad4 OTH exome

AF:

0.00705

GnomAD4 genome

AF:

0.0128

AC:

1946

AN:

152194

Hom.:

Cov.:

AF XY:

0.0126

AC XY:

939

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0369

Gnomad4 AMR

AF:

0.0124

Gnomad4 ASJ

AF:

0.0153

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00194

Gnomad4 OTH

AF:

0.0123

Alfa

AF:

0.00737

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00462

AC:

AN:

3478

EpiCase

AF:

0.00262

EpiControl

AF:

0.00267

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

2.1

DANN

Benign

0.57

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over