Variant 1-225381539-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367479.1(DNAH14):c.13037T>G(p.Phe4346Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 1,538,778 control chromosomes in the GnomAD database, including 313,741 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.55 ( 25900 hom., cov: 32)

Exomes 𝑓: 0.64 ( 287841 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.88

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4610508E-6).

BP6

Variant 1-225381539-T-G is Benign according to our data. Variant chr1-225381539-T-G is described in ClinVar as [Benign]. Clinvar id is 402666.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.749 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.13037T>G	p.Phe4346Cys	missense_variant	81/86	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.13037T>G	p.Phe4346Cys	missense_variant	81/86		NM_001367479.1	ENSP00000508305	P1

Frequencies

GnomAD3 genomes

AF:

0.553

AC:

84032

AN:

151838

Hom.:

25884

Cov.:

show subpopulations

Gnomad AFR

AF:

0.259

Gnomad AMI

AF:

0.551

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.706

Gnomad EAS

AF:

0.769

Gnomad SAS

AF:

0.461

Gnomad FIN

AF:

0.693

Gnomad MID

AF:

0.706

Gnomad NFE

AF:

0.655

Gnomad OTH

AF:

0.602

GnomAD3 exomes

AF:

0.636

AC:

92658

AN:

145582

Hom.:

30704

AF XY:

0.627

AC XY:

48429

AN XY:

77204

show subpopulations

Gnomad AFR exome

AF:

0.255

Gnomad AMR exome

AF:

0.746

Gnomad ASJ exome

AF:

0.706

Gnomad EAS exome

AF:

0.764

Gnomad SAS exome

AF:

0.477

Gnomad FIN exome

AF:

0.690

Gnomad NFE exome

AF:

0.653

Gnomad OTH exome

AF:

0.681

GnomAD4 exome

AF:

0.638

AC:

885049

AN:

1386822

Hom.:

287841

Cov.:

AF XY:

0.634

AC XY:

433778

AN XY:

684102

show subpopulations

Gnomad4 AFR exome

AF:

0.238

Gnomad4 AMR exome

AF:

0.740

Gnomad4 ASJ exome

AF:

0.705

Gnomad4 EAS exome

AF:

0.782

Gnomad4 SAS exome

AF:

0.473

Gnomad4 FIN exome

AF:

0.690

Gnomad4 NFE exome

AF:

0.650

Gnomad4 OTH exome

AF:

0.636

GnomAD4 genome

AF:

0.553

AC:

84065

AN:

151956

Hom.:

25900

Cov.:

AF XY:

0.557

AC XY:

41358

AN XY:

74240

show subpopulations

Gnomad4 AFR

AF:

0.259

Gnomad4 AMR

AF:

0.712

Gnomad4 ASJ

AF:

0.706

Gnomad4 EAS

AF:

0.769

Gnomad4 SAS

AF:

0.462

Gnomad4 FIN

AF:

0.693

Gnomad4 NFE

AF:

0.655

Gnomad4 OTH

AF:

0.608

Alfa

AF:

0.648

Hom.:

82981

Bravo

AF:

0.548

TwinsUK

AF:

0.643

AC:

2384

ALSPAC

AF:

0.656

AC:

2530

ESP6500AA

AF:

0.245

AC:

339

ESP6500EA

AF:

0.657

AC:

2090

ExAC

AF:

0.538

AC:

11275

Asia WGS

AF:

0.589

AC:

2047

AN:

3474

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

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.67

BayesDel_noAF

Benign

-0.59

CADD

Benign

DANN

Benign

0.47

DEOGEN2

Benign

0.030

T;.;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.98

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.64

T;T;.

MetaRNN

Benign

0.0000015

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

L;.;.

MutationTaster

Benign

1.0

P;P;P

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.5

D;D;D

REVEL

Benign

0.069

Sift

Benign

0.15

T;D;D

Sift4G

Uncertain

0.0060

D;D;D

Polyphen

0.0

.;B;B

Vest4

0.26

ClinPred

0.015

GERP RS

1.2

Varity_R

0.15

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