dbSNP rs41267349: DNAH14:p.Pro147Arg (chr1-224964551-C-G) – 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.440C>G(p.Pro147Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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. P147L) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.607

Publications

7 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:

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=0.14527333).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH14	NM_001367479.1	MANE Select	c.440C>G	p.Pro147Arg	missense	Exon 5 of 86	NP_001354408.1	A0A804HLD3
DNAH14	NM_001145154.3		c.440C>G	p.Pro147Arg	missense	Exon 5 of 11	NP_001138626.1	Q0VDD8-2
DNAH14	NM_001349911.2		c.440C>G	p.Pro147Arg	missense	Exon 5 of 11	NP_001336840.1	M9MMK7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH14	ENST00000682510.1	MANE Select	c.440C>G	p.Pro147Arg	missense	Exon 5 of 86	ENSP00000508305.1	A0A804HLD3
DNAH14	ENST00000400952.7	TSL:1	c.440C>G	p.Pro147Arg	missense	Exon 5 of 11	ENSP00000383737.3	Q0VDD8-2
DNAH14	ENST00000366849.5	TSL:1	c.440C>G	p.Pro147Arg	missense	Exon 5 of 11	ENSP00000355814.1	M9MMK7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1456186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724276

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33388

American (AMR)

AF:

0.0000224

AC:

AN:

44572

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26002

East Asian (EAS)

AF:

0.00

AC:

AN:

39482

South Asian (SAS)

AF:

0.00

AC:

AN:

85066

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53182

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5726

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108690

Other (OTH)

AF:

0.00

AC:

AN:

60078

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

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.49

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.9

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.011

Eigen

Benign

-0.38

Eigen_PC

Benign

-0.49

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.65

M_CAP

Benign

0.017

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

PhyloP100

0.61

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.088

Sift

Benign

0.038

Sift4G

Uncertain

0.021

Polyphen

0.87

Vest4

0.29

MutPred

0.53

Gain of MoRF binding (P = 0.001)

MVP

0.35

MPC

0.24

ClinPred

0.84

GERP RS

0.60

Varity_R

0.10

gMVP

0.19

Mutation Taster

=100/0

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over