Variant rs61748602 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001206927.2(DNAH8):c.4084-4G>T 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 0.00624 in 1,575,248 control chromosomes in the GnomAD database, including 51 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0053 ( 2 hom., cov: 31)

Exomes 𝑓: 0.0063 ( 49 hom. )

Consequence

DNAH8
NM_001206927.2 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0002234

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.436

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 6-38828180-G-T is Benign according to our data. Variant chr6-38828180-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 238645.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00526 (801/152190) while in subpopulation NFE AF= 0.00697 (474/67972). AF 95% confidence interval is 0.00645. There are 2 homozygotes in gnomad4. There are 403 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2 linkuse as main transcript	c.4084-4G>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11 linkuse as main transcript	c.4084-4G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7 linkuse as main transcript	c.3433-4G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	2		ENSP00000352312	A2	Q96JB1-1
DNAH8	ENST00000449981.6 linkuse as main transcript	c.4084-4G>T	splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant	5		ENSP00000415331

Frequencies

GnomAD3 genomes

AF:

0.00527

AC:

801

AN:

152072

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00426

Gnomad ASJ

AF:

0.0210

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.0123

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00697

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00611

AC:

1403

AN:

229690

Hom.:

AF XY:

0.00621

AC XY:

771

AN XY:

124168

show subpopulations

Gnomad AFR exome

AF:

0.000791

Gnomad AMR exome

AF:

0.00314

Gnomad ASJ exome

AF:

0.0196

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00179

Gnomad FIN exome

AF:

0.0144

Gnomad NFE exome

AF:

0.00665

Gnomad OTH exome

AF:

0.00797

GnomAD4 exome

AF:

0.00634

AC:

9026

AN:

1423058

Hom.:

Cov.:

AF XY:

0.00634

AC XY:

4485

AN XY:

707444

show subpopulations

Gnomad4 AFR exome

AF:

0.000345

Gnomad4 AMR exome

AF:

0.00330

Gnomad4 ASJ exome

AF:

0.0180

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00189

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.00642

Gnomad4 OTH exome

AF:

0.00753

GnomAD4 genome

AF:

0.00526

AC:

801

AN:

152190

Hom.:

Cov.:

AF XY:

0.00542

AC XY:

403

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.00425

Gnomad4 ASJ

AF:

0.0210

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.0123

Gnomad4 NFE

AF:

0.00697

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.00656

Hom.:

Bravo

AF:

0.00478

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 25, 2024

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2024

DNAH8: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

7.2

DANN

Benign

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00022

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.34

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.34

Position offset: 27

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