1-225374683-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001367479.1(DNAH14):​c.12319-5C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.814 in 1,540,378 control chromosomes in the GnomAD database, including 518,046 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 43761 hom., cov: 31)
Exomes 𝑓: 0.82 ( 474285 hom. )

Consequence

DNAH14
NM_001367479.1 splice_region, intron

Scores

2
Splicing: ADA: 0.00002266
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -2.41
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 -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.88).
BP6
Variant 1-225374683-C-T is Benign according to our data. Variant chr1-225374683-C-T is described in ClinVar as [Benign]. Clinvar id is 402663.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.934 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNAH14NM_001367479.1 linkc.12319-5C>T splice_region_variant, intron_variant Intron 77 of 85 ENST00000682510.1 NP_001354408.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNAH14ENST00000682510.1 linkc.12319-5C>T splice_region_variant, intron_variant Intron 77 of 85 NM_001367479.1 ENSP00000508305.1 A0A804HLD3

Frequencies

GnomAD3 genomes
AF:
0.737
AC:
111921
AN:
151946
Hom.:
43744
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.452
Gnomad AMI
AF:
0.767
Gnomad AMR
AF:
0.861
Gnomad ASJ
AF:
0.853
Gnomad EAS
AF:
0.956
Gnomad SAS
AF:
0.694
Gnomad FIN
AF:
0.862
Gnomad MID
AF:
0.858
Gnomad NFE
AF:
0.840
Gnomad OTH
AF:
0.786
GnomAD3 exomes
AF:
0.812
AC:
123258
AN:
151766
Hom.:
51071
AF XY:
0.806
AC XY:
64949
AN XY:
80568
show subpopulations
Gnomad AFR exome
AF:
0.444
Gnomad AMR exome
AF:
0.871
Gnomad ASJ exome
AF:
0.859
Gnomad EAS exome
AF:
0.954
Gnomad SAS exome
AF:
0.694
Gnomad FIN exome
AF:
0.856
Gnomad NFE exome
AF:
0.836
Gnomad OTH exome
AF:
0.849
GnomAD4 exome
AF:
0.823
AC:
1142557
AN:
1388314
Hom.:
474285
Cov.:
36
AF XY:
0.820
AC XY:
561059
AN XY:
683934
show subpopulations
Gnomad4 AFR exome
AF:
0.433
Gnomad4 AMR exome
AF:
0.871
Gnomad4 ASJ exome
AF:
0.859
Gnomad4 EAS exome
AF:
0.964
Gnomad4 SAS exome
AF:
0.694
Gnomad4 FIN exome
AF:
0.859
Gnomad4 NFE exome
AF:
0.835
Gnomad4 OTH exome
AF:
0.821
GnomAD4 genome
AF:
0.736
AC:
111977
AN:
152064
Hom.:
43761
Cov.:
31
AF XY:
0.738
AC XY:
54864
AN XY:
74334
show subpopulations
Gnomad4 AFR
AF:
0.452
Gnomad4 AMR
AF:
0.861
Gnomad4 ASJ
AF:
0.853
Gnomad4 EAS
AF:
0.957
Gnomad4 SAS
AF:
0.694
Gnomad4 FIN
AF:
0.862
Gnomad4 NFE
AF:
0.840
Gnomad4 OTH
AF:
0.790
Alfa
AF:
0.823
Hom.:
65648
Bravo
AF:
0.727
Asia WGS
AF:
0.821
AC:
2854
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Mar 28, 2016
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.88
CADD
Benign
0.59
DANN
Benign
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000023
dbscSNV1_RF
Benign
0.0060
SpliceAI score (max)
0.040
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: rs10915816; hg19: chr1-225562385; API