Variant 1-225377371-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.12651C>T(p.Gly4217Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.578 in 1,549,410 control chromosomes in the GnomAD database, including 267,068 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.51 ( 22033 hom., cov: 31)

Exomes 𝑓: 0.59 ( 245035 hom. )

Consequence

DNAH14
NM_001367479.1 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.636

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=-0.66).

BP6

Variant 1-225377371-C-T is Benign according to our data. Variant chr1-225377371-C-T is described in ClinVar as [Benign]. Clinvar id is 402665.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.636 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.723 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH14	NM_001367479.1 link	c.12651C>T	p.Gly4217Gly	synonymous_variant	79/86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH14	ENST00000682510.1 link	c.12651C>T	p.Gly4217Gly	synonymous_variant	79/86		NM_001367479.1	ENSP00000508305.1		A0A804HLD3

Frequencies

GnomAD3 genomes

AF:

0.509

AC:

77373

AN:

151888

Hom.:

22032

Cov.:

show subpopulations

Gnomad AFR

AF:

0.236

Gnomad AMI

AF:

0.519

Gnomad AMR

AF:

0.679

Gnomad ASJ

AF:

0.662

Gnomad EAS

AF:

0.742

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.605

Gnomad MID

AF:

0.646

Gnomad NFE

AF:

0.602

Gnomad OTH

AF:

0.558

GnomAD3 exomes

AF:

0.584

AC:

89204

AN:

152646

Hom.:

27509

AF XY:

0.572

AC XY:

46329

AN XY:

81042

show subpopulations

Gnomad AFR exome

AF:

0.232

Gnomad AMR exome

AF:

0.714

Gnomad ASJ exome

AF:

0.663

Gnomad EAS exome

AF:

0.743

Gnomad SAS exome

AF:

0.406

Gnomad FIN exome

AF:

0.603

Gnomad NFE exome

AF:

0.599

Gnomad OTH exome

AF:

0.620

GnomAD4 exome

AF:

0.586

AC:

818789

AN:

1397404

Hom.:

245035

Cov.:

AF XY:

0.581

AC XY:

400591

AN XY:

689168

show subpopulations

Gnomad4 AFR exome

AF:

0.216

Gnomad4 AMR exome

AF:

0.710

Gnomad4 ASJ exome

AF:

0.663

Gnomad4 EAS exome

AF:

0.751

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.607

Gnomad4 NFE exome

AF:

0.597

Gnomad4 OTH exome

AF:

0.585

GnomAD4 genome

AF:

0.509

AC:

77386

AN:

152006

Hom.:

22033

Cov.:

AF XY:

0.512

AC XY:

38006

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.236

Gnomad4 AMR

AF:

0.679

Gnomad4 ASJ

AF:

0.662

Gnomad4 EAS

AF:

0.743

Gnomad4 SAS

AF:

0.399

Gnomad4 FIN

AF:

0.605

Gnomad4 NFE

AF:

0.602

Gnomad4 OTH

AF:

0.557

Alfa

AF:

0.546

Hom.:

11599

Bravo

AF:

0.510

Asia WGS

AF:

0.525

AC:

1828

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

-0.66

CADD

Benign

2.2

DANN

Benign

0.23

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