chr17-7797394-C-T

Variant summary

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

The NM_020877.5(DNAH2):​c.7950-6C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.613 in 1,613,764 control chromosomes in the GnomAD database, including 307,714 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 23875 hom., cov: 31)
Exomes 𝑓: 0.62 ( 283839 hom. )

Consequence

DNAH2
NM_020877.5 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0001956
2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.01
Variant links:
Genes affected
DNAH2 (HGNC:2948): (dynein axonemal heavy chain 2) Dyneins are microtubule-associated motor protein complexes composed of several heavy, light, and intermediate chains. The axonemal dyneins, found in cilia and flagella, are components of the outer and inner dynein arms attached to the peripheral microtubule doublets. DNAH2 is an axonemal inner arm dynein heavy chain (Chapelin et al., 1997 [PubMed 9256245]).[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=-0.74).
BP6
Variant 17-7797394-C-T is Benign according to our data. Variant chr17-7797394-C-T is described in ClinVar as [Benign]. Clinvar id is 402710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.625 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH2NM_020877.5 linkuse as main transcriptc.7950-6C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000572933.6 NP_065928.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH2ENST00000572933.6 linkuse as main transcriptc.7950-6C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 2 NM_020877.5 ENSP00000458355 P1Q9P225-1
DNAH2ENST00000389173.6 linkuse as main transcriptc.7950-6C>T splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 2 ENSP00000373825 P1Q9P225-1

Frequencies

GnomAD3 genomes
AF:
0.542
AC:
82263
AN:
151872
Hom.:
23865
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.315
Gnomad AMI
AF:
0.666
Gnomad AMR
AF:
0.635
Gnomad ASJ
AF:
0.588
Gnomad EAS
AF:
0.625
Gnomad SAS
AF:
0.620
Gnomad FIN
AF:
0.646
Gnomad MID
AF:
0.516
Gnomad NFE
AF:
0.626
Gnomad OTH
AF:
0.558
GnomAD3 exomes
AF:
0.612
AC:
153822
AN:
251384
Hom.:
48030
AF XY:
0.613
AC XY:
83284
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.309
Gnomad AMR exome
AF:
0.701
Gnomad ASJ exome
AF:
0.586
Gnomad EAS exome
AF:
0.633
Gnomad SAS exome
AF:
0.614
Gnomad FIN exome
AF:
0.639
Gnomad NFE exome
AF:
0.622
Gnomad OTH exome
AF:
0.602
GnomAD4 exome
AF:
0.620
AC:
906534
AN:
1461774
Hom.:
283839
Cov.:
64
AF XY:
0.620
AC XY:
450713
AN XY:
727194
show subpopulations
Gnomad4 AFR exome
AF:
0.304
Gnomad4 AMR exome
AF:
0.696
Gnomad4 ASJ exome
AF:
0.581
Gnomad4 EAS exome
AF:
0.604
Gnomad4 SAS exome
AF:
0.614
Gnomad4 FIN exome
AF:
0.645
Gnomad4 NFE exome
AF:
0.629
Gnomad4 OTH exome
AF:
0.605
GnomAD4 genome
AF:
0.541
AC:
82294
AN:
151990
Hom.:
23875
Cov.:
31
AF XY:
0.548
AC XY:
40665
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.315
Gnomad4 AMR
AF:
0.635
Gnomad4 ASJ
AF:
0.588
Gnomad4 EAS
AF:
0.625
Gnomad4 SAS
AF:
0.619
Gnomad4 FIN
AF:
0.646
Gnomad4 NFE
AF:
0.626
Gnomad4 OTH
AF:
0.557
Alfa
AF:
0.594
Hom.:
35518
Bravo
AF:
0.532
Asia WGS
AF:
0.618
AC:
2146
AN:
3478
EpiCase
AF:
0.608
EpiControl
AF:
0.607

ClinVar

Significance: Benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingLaboratory for Molecular Medicine, Mass General Brigham Personalized MedicineMar 29, 2016Variant 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 -
DNAH2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
not provided Benign:1
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.74
CADD
Benign
15
DANN
Benign
0.57

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00020
dbscSNV1_RF
Benign
0.024
SpliceAI score (max)
0.23
Details are displayed if max score is > 0.2
DS_AG_spliceai
0.23
Position offset: -8

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: rs1565817; hg19: chr17-7700712; COSMIC: COSV66719970; API