Genetic Variant DNAH14:p.Lys1010Met (chr1-225080641-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367479.1(DNAH14):c.3029A>T(p.Lys1010Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K1010R) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.598

Publications

21 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: LIMITED Submitted by: G2P

DNAH14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.109030664).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH14	NM_001367479.1 link	c.3029A>T	p.Lys1010Met	missense_variant	Exon 19 of 86	ENST00000682510.1	NP_001354408.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DNAH14	ENST00000682510.1 link	c.3029A>T	p.Lys1010Met	missense_variant	Exon 19 of 86		NM_001367479.1	ENSP00000508305.1	A0A804HLD3
DNAH14	ENST00000430092.5 link	c.3029A>T	p.Lys1010Met	missense_variant	Exon 19 of 84	5		ENSP00000414402.1	Q0VDD8-4
DNAH14	ENST00000439375.6 link	c.3029A>T	p.Lys1010Met	missense_variant	Exon 18 of 83	5		ENSP00000392061.2	Q0VDD8-4
DNAH14	ENST00000445597.6 link	c.2831A>T	p.Lys944Met	missense_variant	Exon 15 of 61	5		ENSP00000409472.2	Q0VDD8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1399634

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690298

African (AFR)

AF:

0.00

AC:

AN:

31596

American (AMR)

AF:

0.00

AC:

AN:

35708

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25178

East Asian (EAS)

AF:

0.00

AC:

AN:

35722

South Asian (SAS)

AF:

0.00

AC:

AN:

79224

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1079006

Other (OTH)

AF:

0.00

AC:

AN:

58082

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.52

CADD

Benign

7.5

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0067

T;.;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.015

LIST_S2

Benign

0.30

T;T;.

M_CAP

Benign

0.030

MetaRNN

Benign

0.11

T;T;T

MetaSVM

Benign

-0.97

PhyloP100

-0.60

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.34

N;N;N

REVEL

Benign

0.025

Sift

Benign

0.065

T;T;T

Sift4G

Uncertain

0.027

D;D;D

Polyphen

0.0040

.;B;B

Vest4

0.23

MutPred

0.54

.;Loss of ubiquitination at K1010 (P = 0.0155);Loss of ubiquitination at K1010 (P = 0.0155);

MVP

0.19

ClinPred

0.045

GERP RS

3.2

Varity_R

0.078

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over