Variant 1-224967584-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 3P and 9B. PVS1_ModeratePP3BP6BS1BS2

The NM_001367479.1(DNAH14):c.651+1G>A variant causes a splice donor change. The variant allele was found at a frequency of 0.00199 in 1,599,268 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0025 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 27 hom. )

Consequence

DNAH14
NM_001367479.1 splice_donor

Scores

Splicing: ADA: 1.000

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.45

Variant links:

Genes affected

DNAH14 (HGNC:2945): (dynein axonemal heavy chain 14) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. Two major classes of dyneins, axonemal and cytoplasmic, have been identified. DNAH14 is an axonemal dynein heavy chain (DHC) (Vaughan et al., 1996 [PubMed 8812413]).[supplied by OMIM, Mar 2008]

DNAH14 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.01097156 fraction of the gene. No cryptic splice site detected. Exon removal is inframe change.

PP3

Multiple lines of computational evidence support a deleterious effect 5: Cadd, dbscSNV1_ADA, dbscSNV1_RF, max_spliceai, Eigen [when BayesDel_addAF, MutationTaster was below the threshold]

BP6

Variant 1-224967584-G-A is Benign according to our data. Variant chr1-224967584-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3056432.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00254 (386/151966) while in subpopulation EAS AF= 0.0219 (113/5156). AF 95% confidence interval is 0.0186. There are 4 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1 linkuse as main transcript	c.651+1G>A		splice_donor_variant		ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1 linkuse as main transcript	c.651+1G>A		splice_donor_variant			NM_001367479.1	ENSP00000508305	P1

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

384

AN:

151848

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000701

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0130

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.0219

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000515

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00576

AC:

1354

AN:

235122

Hom.:

AF XY:

0.00441

AC XY:

562

AN XY:

127492

show subpopulations

Gnomad AFR exome

AF:

0.00114

Gnomad AMR exome

AF:

0.0283

Gnomad ASJ exome

AF:

0.00200

Gnomad EAS exome

AF:

0.0220

Gnomad SAS exome

AF:

0.000150

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000476

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.00193

AC:

2800

AN:

1447302

Hom.:

Cov.:

AF XY:

0.00167

AC XY:

1204

AN XY:

719516

show subpopulations

Gnomad4 AFR exome

AF:

0.000523

Gnomad4 AMR exome

AF:

0.0260

Gnomad4 ASJ exome

AF:

0.00148

Gnomad4 EAS exome

AF:

0.0239

Gnomad4 SAS exome

AF:

0.0000970

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000566

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00254

AC:

386

AN:

151966

Hom.:

Cov.:

AF XY:

0.00263

AC XY:

195

AN XY:

74270

show subpopulations

Gnomad4 AFR

AF:

0.000699

Gnomad4 AMR

AF:

0.0131

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.0219

Gnomad4 SAS

AF:

0.000416

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000515

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00164

Hom.:

Bravo

AF:

0.00370

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00111

AC:

ESP6500EA

AF:

0.00111

AC:

ExAC

AF:

0.00514

AC:

621

Asia WGS

AF:

0.00723

AC:

AN:

3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNAH14-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

May 01, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Uncertain

0.080

CADD

Pathogenic

DANN

Uncertain

0.98

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.76

FATHMM_MKL

Uncertain

0.94

MutationTaster

Benign

1.0

D;D;D;D;D;D;D

GERP RS

4.8

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.91

SpliceAI score (max)

0.99

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.99

Position offset: -1

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