rs202094249

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015512.5(DNAH1):ā€‹c.12626A>Gā€‹(p.Gln4209Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000317 in 1,614,022 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.00026 ( 0 hom., cov: 33)
Exomes š‘“: 0.00032 ( 7 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

3
13

Clinical Significance

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

Conservation

PhyloP100: 1.41
Variant links:
Genes affected
DNAH1 (HGNC:2940): (dynein axonemal heavy chain 1) This gene encodes an inner dynein arm heavy chain that provides structural support between the radial spokes and the outer doublet of the sperm tail. Naturally occurring mutations in this gene are associated with primary ciliary dyskinesia and multiple morphological anomalies of the flagella that result in asthenozoospermia and male infertility. Mice with a homozygous knockout of the orthologous gene are viable but have reduced sperm motility and are infertile. [provided by RefSeq, Feb 2017]

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 (MetaRNN=0.004714012).
BP6
Variant 3-52399729-A-G is Benign according to our data. Variant chr3-52399729-A-G is described in ClinVar as [Benign]. Clinvar id is 478410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000324 (473/1461684) while in subpopulation AMR AF= 0.0104 (467/44720). AF 95% confidence interval is 0.00966. There are 7 homozygotes in gnomad4_exome. There are 185 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH1NM_015512.5 linkuse as main transcriptc.12626A>G p.Gln4209Arg missense_variant 77/78 ENST00000420323.7 NP_056327.4 Q9P2D7-4A0A140VJI6
DNAH1XM_017006129.2 linkuse as main transcriptc.12695A>G p.Gln4232Arg missense_variant 79/80 XP_016861618.1
DNAH1XM_017006130.2 linkuse as main transcriptc.12626A>G p.Gln4209Arg missense_variant 78/79 XP_016861619.1 Q9P2D7-4A0A140VJI6
DNAH1XM_017006131.2 linkuse as main transcriptc.12569A>G p.Gln4190Arg missense_variant 78/79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkuse as main transcriptc.12626A>G p.Gln4209Arg missense_variant 77/781 NM_015512.5 ENSP00000401514.2 Q9P2D7-4

Frequencies

GnomAD3 genomes
AF:
0.000256
AC:
39
AN:
152220
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00242
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:
0.00
Gnomad OTH
AF:
0.000956
GnomAD3 exomes
AF:
0.00175
AC:
437
AN:
249144
Hom.:
7
AF XY:
0.00124
AC XY:
168
AN XY:
135172
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0125
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000991
GnomAD4 exome
AF:
0.000324
AC:
473
AN:
1461684
Hom.:
7
Cov.:
32
AF XY:
0.000254
AC XY:
185
AN XY:
727128
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0104
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000994
GnomAD4 genome
AF:
0.000256
AC:
39
AN:
152338
Hom.:
0
Cov.:
33
AF XY:
0.000242
AC XY:
18
AN XY:
74492
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00242
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000946
Alfa
AF:
0.0000735
Hom.:
0
Bravo
AF:
0.000778
ExAC
AF:
0.00136
AC:
164

ClinVar

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

Submissions by phenotype

not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingARUP Laboratories, Molecular Genetics and Genomics, ARUP LaboratoriesMar 09, 2022- -
Spermatogenic failure 18;C4539798:Ciliary dyskinesia, primary, 37 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
AlphaMissense
Benign
0.065
BayesDel_addAF
Benign
-0.59
T
BayesDel_noAF
Benign
-0.61
CADD
Benign
17
DANN
Uncertain
0.99
Eigen
Benign
-0.74
Eigen_PC
Benign
-0.67
FATHMM_MKL
Benign
0.45
N
LIST_S2
Benign
0.48
T
MetaRNN
Benign
0.0047
T
MetaSVM
Benign
-0.94
T
PrimateAI
Benign
0.31
T
PROVEAN
Benign
-1.5
N
REVEL
Benign
0.024
Sift
Uncertain
0.020
D
Sift4G
Uncertain
0.018
D
Vest4
0.20
MVP
0.16
MPC
0.17
ClinPred
0.027
T
GERP RS
2.0
gMVP
0.61

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: rs202094249; hg19: chr3-52433745; COSMIC: COSV56230867; COSMIC: COSV56230867; API