rs72657314

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_001277115.2(DNAH11):​c.4255-7C>G 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 0.000198 in 1,612,668 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0011 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

DNAH11
NM_001277115.2 splice_region, splice_polypyrimidine_tract, intron

Scores

2
Splicing: ADA: 0.0006546
2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.115
Variant links:
Genes affected
DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 7-21619093-C-G is Benign according to our data. Variant chr7-21619093-C-G is described in ClinVar as [Benign]. Clinvar id is 416422.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00106 (162/152132) while in subpopulation AFR AF= 0.00361 (150/41518). AF 95% confidence interval is 0.00314. There are 0 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH11NM_001277115.2 linkuse as main transcriptc.4255-7C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant ENST00000409508.8 NP_001264044.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH11ENST00000409508.8 linkuse as main transcriptc.4255-7C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant 5 NM_001277115.2 ENSP00000475939 P1
DNAH11ENST00000465593.1 linkuse as main transcriptn.281-7C>G splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00105
AC:
160
AN:
152014
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00358
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000524
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:
0.0000294
Gnomad OTH
AF:
0.000958
GnomAD3 exomes
AF:
0.000237
AC:
59
AN:
248566
Hom.:
0
AF XY:
0.000193
AC XY:
26
AN XY:
134860
show subpopulations
Gnomad AFR exome
AF:
0.00304
Gnomad AMR exome
AF:
0.000291
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000887
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000108
AC:
158
AN:
1460536
Hom.:
0
Cov.:
30
AF XY:
0.0000977
AC XY:
71
AN XY:
726536
show subpopulations
Gnomad4 AFR exome
AF:
0.00354
Gnomad4 AMR exome
AF:
0.000270
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000581
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.000282
GnomAD4 genome
AF:
0.00106
AC:
162
AN:
152132
Hom.:
0
Cov.:
32
AF XY:
0.00110
AC XY:
82
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00361
Gnomad4 AMR
AF:
0.000524
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000948
Alfa
AF:
0.000307
Hom.:
0
Bravo
AF:
0.00111

ClinVar

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

Submissions by phenotype

Primary ciliary dyskinesia Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJan 25, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.34
DANN
Benign
0.55

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.00065
dbscSNV1_RF
Benign
0.058
SpliceAI score (max)
0.090
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: rs72657314; hg19: chr7-21658711; API