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GeneBe

1-224952757-G-T

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBS1BS2

The NM_001367479.1(DNAH14):c.55G>T(p.Glu19Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00187 in 1,600,652 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.010 ( 21 hom., cov: 32)
Exomes 𝑓: 0.0010 ( 19 hom. )

Consequence

DNAH14
NM_001367479.1 stop_gained

Scores

2
5

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.577
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM4
?
    PM4 - Protein length changes as a result of in-frame deletions/insertions in a nonrepeat region or stop-loss variants
Stoplost variant in NM_001367479.1 Downstream stopcodon found after 4681 codons.
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 1-224952757-G-T is Benign according to our data. Variant chr1-224952757-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 3033978.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.01 (1522/152268) while in subpopulation AFR AF= 0.0346 (1437/41542). AF 95% confidence interval is 0.0331. There are 21 homozygotes in gnomad4. There are 707 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 21 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DNAH14NM_001367479.1 linkuse as main transcriptc.55G>T p.Glu19Ter stop_gained 2/86 ENST00000682510.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DNAH14ENST00000682510.1 linkuse as main transcriptc.55G>T p.Glu19Ter stop_gained 2/86 NM_001367479.1 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00999
AC:
1520
AN:
152150
Hom.:
21
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0346
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00314
Gnomad ASJ
AF:
0.000865
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.000191
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00228
AC:
527
AN:
231152
Hom.:
6
AF XY:
0.00166
AC XY:
208
AN XY:
125134
show subpopulations
Gnomad AFR exome
AF:
0.0317
Gnomad AMR exome
AF:
0.00180
Gnomad ASJ exome
AF:
0.000316
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000359
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000963
Gnomad OTH exome
AF:
0.00140
GnomAD4 exome
AF:
0.00102
AC:
1474
AN:
1448384
Hom.:
19
Cov.:
29
AF XY:
0.000906
AC XY:
652
AN XY:
719694
show subpopulations
Gnomad4 AFR exome
AF:
0.0342
Gnomad4 AMR exome
AF:
0.00222
Gnomad4 ASJ exome
AF:
0.000350
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000239
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000103
Gnomad4 OTH exome
AF:
0.00204
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0100
AC:
1522
AN:
152268
Hom.:
21
Cov.:
32
AF XY:
0.00949
AC XY:
707
AN XY:
74462
show subpopulations
Gnomad4 AFR
AF:
0.0346
Gnomad4 AMR
AF:
0.00307
Gnomad4 ASJ
AF:
0.000865
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000191
Gnomad4 OTH
AF:
0.00993
Alfa
AF:
0.0235
Hom.:
2351
Bravo
AF:
0.0112
ESP6500AA
AF:
0.0344
AC:
124
ESP6500EA
AF:
0.00
AC:
0
ExAC
?
    Exome Aggregation Consortium database
AF:
0.00273
AC:
330
Asia WGS
AF:
0.00173
AC:
7
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

DNAH14-related disorder Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesAug 04, 2023This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.18
T
BayesDel_noAF
Uncertain
-0.010
Cadd
Pathogenic
31
Dann
Uncertain
0.99
Eigen
Benign
0.066
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.039
N
MutationTaster
Benign
1.0
A;A;A;A;A;A;A
Vest4
0.15
GERP RS
-0.72

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.

Other links and lift over

dbSNP: rs61745064; hg19: chr1-225140459; COSMIC: COSV64782115; COSMIC: COSV64782115; API