Variant rs139673856 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001206927.2(DNAH8):c.11817-7G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000266 in 1,582,992 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

DNAH8
NM_001206927.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00008540

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.116

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 -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 6-38938791-G-A is Benign according to our data. Variant chr6-38938791-G-A is described in ClinVar as [Benign]. Clinvar id is 414386.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00145 (221/152268) while in subpopulation AFR AF= 0.0051 (212/41544). AF 95% confidence interval is 0.00454. There are 1 homozygotes in gnomad4. There are 98 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.11817-7G>A		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000327475.11	NP_001193856.1
DNAH8-AS1	NR_038401.1 linkuse as main transcript	n.61-2399C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.11817-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_001206927.2	ENSP00000333363	P2
DNAH8-AS1	ENST00000416948.1 linkuse as main transcript	n.53-2399C>T	intron_variant, non_coding_transcript_variant	2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.11166-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.11817-7G>A	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.00147

AC:

223

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00517

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000342

AC:

AN:

234214

Hom.:

AF XY:

0.000197

AC XY:

AN XY:

126826

show subpopulations

Gnomad AFR exome

AF:

0.00467

Gnomad AMR exome

AF:

0.000134

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000924

Gnomad OTH exome

AF:

0.000177

GnomAD4 exome

AF:

0.000140

AC:

200

AN:

1430724

Hom.:

Cov.:

AF XY:

0.000120

AC XY:

AN XY:

710818

show subpopulations

Gnomad4 AFR exome

AF:

0.00530

Gnomad4 AMR exome

AF:

0.000127

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000365

Gnomad4 OTH exome

AF:

0.000305

GnomAD4 genome

AF:

0.00145

AC:

221

AN:

152268

Hom.:

Cov.:

AF XY:

0.00132

AC XY:

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.00510

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000738

Hom.:

Bravo

AF:

0.00165

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Labcorp Genetics (formerly Invitae), Labcorp

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.32

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000085

dbscSNV1_RF

Benign

0.010

SpliceAI score (max)

0.070

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