dbSNP rs202149727: DNAH14:p.Tyr119Cys (chr1-224960291-A-G) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001367479.1(DNAH14):c.356A>G(p.Tyr119Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000375 in 1,599,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

DNAH14
NM_001367479.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.609

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30969188).

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.356A>G	p.Tyr119Cys	missense	Exon 4 of 86	NP_001354408.1	A0A804HLD3
DNAH14	NM_001145154.3		c.356A>G	p.Tyr119Cys	missense	Exon 4 of 11	NP_001138626.1	Q0VDD8-2
DNAH14	NM_001349911.2		c.356A>G	p.Tyr119Cys	missense	Exon 4 of 11	NP_001336840.1	M9MMK7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNAH14	ENST00000682510.1	MANE Select	c.356A>G	p.Tyr119Cys	missense	Exon 4 of 86	ENSP00000508305.1	A0A804HLD3
DNAH14	ENST00000400952.7	TSL:1	c.356A>G	p.Tyr119Cys	missense	Exon 4 of 11	ENSP00000383737.3	Q0VDD8-2
DNAH14	ENST00000366849.5	TSL:1	c.356A>G	p.Tyr119Cys	missense	Exon 4 of 11	ENSP00000355814.1	M9MMK7

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000858

AC:

AN:

233032

AF XY:

0.0000790

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000983

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000233

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000743

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000401

AC:

AN:

1447708

Hom.:

Cov.:

AF XY:

0.0000500

AC XY:

AN XY:

719976

show subpopulations

African (AFR)

AF:

0.0000611

AC:

AN:

32738

American (AMR)

AF:

0.0000724

AC:

AN:

41414

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25316

East Asian (EAS)

AF:

0.000203

AC:

AN:

39466

South Asian (SAS)

AF:

0.000144

AC:

AN:

83314

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.0000253

AC:

AN:

1106964

Other (OTH)

AF:

0.0000837

AC:

AN:

59754

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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

AF:

0.0000131

AC:

AN:

152142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74322

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41448

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68006

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000966

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000497

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.85

Eigen

Benign

0.14

Eigen_PC

Benign

0.024

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.81

M_CAP

Pathogenic

0.30

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.72

PhyloP100

0.61

PrimateAI

Benign

0.48

PROVEAN

Uncertain

-4.1

REVEL

Benign

0.15

Sift

Uncertain

0.022

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.37

MVP

0.58

MPC

0.094

ClinPred

0.22

GERP RS

3.0

gMVP

0.058

Mutation Taster

=94/6

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over