Variant 1-224968765-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001367479.1(DNAH14):c.658A>G(p.Asn220Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000764 in 1,309,114 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08906156).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH14	NM_001367479.1 linkuse as main transcript	c.658A>G	p.Asn220Asp	missense_variant	7/86	ENST00000682510.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH14	ENST00000682510.1 linkuse as main transcript	c.658A>G	p.Asn220Asp	missense_variant	7/86		NM_001367479.1	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000947

AC:

AN:

105564

Hom.:

AF XY:

0.0000177

AC XY:

AN XY:

56636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000169

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.64e-7

AC:

AN:

1309114

Hom.:

Cov.:

AF XY:

0.00000155

AC XY:

AN XY:

646552

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000313

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 14, 2022

The c.658A>G (p.N220D) alteration is located in exon 7 (coding exon 6) of the DNAH14 gene. This alteration results from a A to G substitution at nucleotide position 658, causing the asparagine (N) at amino acid position 220 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.73

Cadd

Benign

Dann

Benign

0.96

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.54

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.29

T;T;T;.

M_CAP

Benign

0.031

MetaRNN

Benign

0.089

T;T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

N;N;N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.094

Sift

Benign

0.29

T;T;T;T

Sift4G

Benign

0.26

T;T;T;T

Polyphen

0.19

B;B;.;B

Vest4

0.12

MutPred

0.41

Gain of ubiquitination at K217 (P = 0.0725);Gain of ubiquitination at K217 (P = 0.0725);.;Gain of ubiquitination at K217 (P = 0.0725);

MVP

0.072

MPC

0.075

ClinPred

0.21

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.019

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