Variant 1-225042906-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001367479.1(DNAH14):c.1560C>T(p.Cys520=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.917 in 1,551,486 control chromosomes in the GnomAD database, including 663,421 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 51686 hom., cov: 31)

Exomes 𝑓: 0.93 ( 611735 hom. )

Consequence

DNAH14
NM_001367479.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.314

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 1-225042906-C-T is Benign according to our data. Variant chr1-225042906-C-T is described in ClinVar as [Benign]. Clinvar id is 402644.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.314 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.956 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1 linkuse as main transcript	c.1560C>T	p.Cys520=	synonymous_variant	13/86	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.1560C>T	p.Cys520=	synonymous_variant	13/86		NM_001367479.1	ENSP00000508305	P1
DNAH14	ENST00000430092.5 linkuse as main transcript	c.1560C>T	p.Cys520=	synonymous_variant	13/84	5		ENSP00000414402		Q0VDD8-4
DNAH14	ENST00000439375.6 linkuse as main transcript	c.1560C>T	p.Cys520=	synonymous_variant	12/83	5		ENSP00000392061		Q0VDD8-4
DNAH14	ENST00000445597.6 linkuse as main transcript	c.1617C>T	p.Cys539=	synonymous_variant	11/61	5		ENSP00000409472		Q0VDD8-1

Frequencies

GnomAD3 genomes

AF:

0.797

AC:

121134

AN:

152008

Hom.:

51668

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.980

Gnomad AMR

AF:

0.796

Gnomad ASJ

AF:

0.916

Gnomad EAS

AF:

0.710

Gnomad SAS

AF:

0.850

Gnomad FIN

AF:

0.968

Gnomad MID

AF:

0.845

Gnomad NFE

AF:

0.962

Gnomad OTH

AF:

0.823

GnomAD3 exomes

AF:

0.869

AC:

136548

AN:

157066

Hom.:

60738

AF XY:

0.879

AC XY:

73038

AN XY:

83116

show subpopulations

Gnomad AFR exome

AF:

0.469

Gnomad AMR exome

AF:

0.759

Gnomad ASJ exome

AF:

0.927

Gnomad EAS exome

AF:

0.702

Gnomad SAS exome

AF:

0.868

Gnomad FIN exome

AF:

0.969

Gnomad NFE exome

AF:

0.960

Gnomad OTH exome

AF:

0.889

GnomAD4 exome

AF:

0.930

AC:

1301811

AN:

1399360

Hom.:

611735

Cov.:

AF XY:

0.931

AC XY:

642256

AN XY:

690180

show subpopulations

Gnomad4 AFR exome

AF:

0.451

Gnomad4 AMR exome

AF:

0.766

Gnomad4 ASJ exome

AF:

0.926

Gnomad4 EAS exome

AF:

0.724

Gnomad4 SAS exome

AF:

0.869

Gnomad4 FIN exome

AF:

0.968

Gnomad4 NFE exome

AF:

0.962

Gnomad4 OTH exome

AF:

0.894

GnomAD4 genome

AF:

0.797

AC:

121186

AN:

152126

Hom.:

51686

Cov.:

AF XY:

0.796

AC XY:

59240

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.470

Gnomad4 AMR

AF:

0.796

Gnomad4 ASJ

AF:

0.916

Gnomad4 EAS

AF:

0.710

Gnomad4 SAS

AF:

0.852

Gnomad4 FIN

AF:

0.968

Gnomad4 NFE

AF:

0.962

Gnomad4 OTH

AF:

0.823

Alfa

AF:

0.894

Hom.:

43302

Bravo

AF:

0.768

Asia WGS

AF:

0.752

AC:

2618

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

7.9

DANN

Benign

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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