Genetic Variant DNAH14:p.Lys3567Gln (chr1-225345982-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001367479.1(DNAH14):c.10699A>C(p.Lys3567Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,397,614 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 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. K3567E) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.23

Publications

0 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
primary ciliary dyskinesia
Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

DNAH14 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.043444514).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367479.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH14	NM_001367479.1	MANE Select	c.10699A>C	p.Lys3567Gln	missense	Exon 70 of 86	NP_001354408.1	A0A804HLD3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH14	ENST00000682510.1	MANE Select	c.10699A>C	p.Lys3567Gln	missense	Exon 70 of 86	ENSP00000508305.1	A0A804HLD3
DNAH14	ENST00000327794.10	TSL:1	n.3595A>C		non_coding_transcript_exon	Exon 26 of 40	ENSP00000328980.6	H7BXS7
DNAH14	ENST00000430092.5	TSL:5	c.10420A>C	p.Lys3474Gln	missense	Exon 68 of 84	ENSP00000414402.1	Q0VDD8-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000215

AC:

AN:

1397614

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689456

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31352

American (AMR)

AF:

0.00

AC:

AN:

35228

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25070

East Asian (EAS)

AF:

0.00

AC:

AN:

35728

South Asian (SAS)

AF:

0.00

AC:

AN:

79134

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49236

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5694

European-Non Finnish (NFE)

AF:

9.27e-7

AC:

AN:

1078300

Other (OTH)

AF:

0.0000173

AC:

AN:

57872

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.89

DEOGEN2

Benign

0.0032

Eigen

Benign

-0.66

Eigen_PC

Benign

-0.64

FATHMM_MKL

Benign

0.25

LIST_S2

Benign

0.63

M_CAP

Benign

0.029

MetaRNN

Benign

0.043

MetaSVM

Benign

-0.93

PhyloP100

2.2

PrimateAI

Benign

0.45

PROVEAN

Benign

0.37

REVEL

Benign

0.022

Sift

Benign

0.44

Sift4G

Uncertain

0.030

Polyphen

0.15

Vest4

0.052

MutPred

0.26

Loss of ubiquitination at K3474 (P = 0.0161)

MVP

0.17

ClinPred

0.078

GERP RS

3.4

Varity_R

0.052

Mutation Taster

=99/1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over