Variant 1-224952757-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 4P and 9B. PVS1_StrongBP6BS1BS2

The NM_001367479.1(DNAH14):c.55G>T(p.Glu19*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,600,652 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.010 ( 21 hom., cov: 32)

Exomes 𝑓: 0.0010 ( 19 hom. )

Consequence

DNAH14
NM_001367479.1 stop_gained

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.577

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 -5 ACMG points.

PVS1

Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.996 CDS is truncated, and there are 3 pathogenic variants in the truncated region.

BP6

Variant 1-224952757-G-T is Benign according to our data. Variant chr1-224952757-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3033978.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1522/152268) while in subpopulation AFR AF= 0.0346 (1437/41542). AF 95% confidence interval is 0.0331. There are 21 homozygotes in gnomad4. There are 707 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1 link	c.55G>T	p.Glu19*	stop_gained	Exon 2 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1 link	c.55G>T	p.Glu19*	stop_gained	Exon 2 of 86		NM_001367479.1	ENSP00000508305.1		A0A804HLD3

Frequencies

GnomAD3 genomes

AF:

0.00999

AC:

1520

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0346

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00314

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00228

AC:

527

AN:

231152

Hom.:

AF XY:

0.00166

AC XY:

208

AN XY:

125134

show subpopulations

Gnomad AFR exome

AF:

0.0317

Gnomad AMR exome

AF:

0.00180

Gnomad ASJ exome

AF:

0.000316

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000963

Gnomad OTH exome

AF:

0.00140

GnomAD4 exome

AF:

0.00102

AC:

1474

AN:

1448384

Hom.:

Cov.:

AF XY:

0.000906

AC XY:

652

AN XY:

719694

show subpopulations

Gnomad4 AFR exome

AF:

0.0342

Gnomad4 AMR exome

AF:

0.00222

Gnomad4 ASJ exome

AF:

0.000350

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000239

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.0100

AC:

1522

AN:

152268

Hom.:

Cov.:

AF XY:

0.00949

AC XY:

707

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0346

Gnomad4 AMR

AF:

0.00307

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.0235

Hom.:

2351

Bravo

AF:

0.0112

ESP6500AA

AF:

0.0344

AC:

124

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00273

AC:

330

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DNAH14-related disorder

Benign:1

Aug 04, 2023

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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

-0.18

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

0.99

Eigen

Benign

0.066

Eigen_PC

Benign

-0.35

FATHMM_MKL

Benign

0.039

Vest4

0.15

GERP RS

-0.72

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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