rs376991251

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015512.5(DNAH1):ā€‹c.1986C>Gā€‹(p.Asp662Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000691 in 1,448,200 control chromosomes in the GnomAD database, with no homozygous occurrence. 11/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 6.9e-7 ( 0 hom. )

Consequence

DNAH1
NM_015512.5 missense

Scores

4
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.574
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DNAH1NM_015512.5 linkuse as main transcriptc.1986C>G p.Asp662Glu missense_variant 12/78 ENST00000420323.7 NP_056327.4 Q9P2D7-4A0A140VJI6
DNAH1XM_017006129.2 linkuse as main transcriptc.1986C>G p.Asp662Glu missense_variant 13/80 XP_016861618.1
DNAH1XM_017006130.2 linkuse as main transcriptc.1986C>G p.Asp662Glu missense_variant 13/79 XP_016861619.1 Q9P2D7-4A0A140VJI6
DNAH1XM_017006131.2 linkuse as main transcriptc.1986C>G p.Asp662Glu missense_variant 13/79 XP_016861620.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DNAH1ENST00000420323.7 linkuse as main transcriptc.1986C>G p.Asp662Glu missense_variant 12/781 NM_015512.5 ENSP00000401514.2 Q9P2D7-4
DNAH1ENST00000486752.5 linkuse as main transcriptn.2247C>G non_coding_transcript_exon_variant 12/772
DNAH1ENST00000497875.1 linkuse as main transcriptn.2151C>G non_coding_transcript_exon_variant 13/212

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.91e-7
AC:
1
AN:
1448200
Hom.:
0
Cov.:
31
AF XY:
0.00000139
AC XY:
1
AN XY:
718792
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
9.05e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.22
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.47
CADD
Benign
20
DANN
Uncertain
0.98
Eigen
Benign
-0.099
Eigen_PC
Benign
-0.0020
FATHMM_MKL
Uncertain
0.87
D
LIST_S2
Benign
0.77
T
M_CAP
Benign
0.014
T
MetaRNN
Uncertain
0.50
D
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
0.98
D
PrimateAI
Uncertain
0.63
T
PROVEAN
Benign
-1.6
N
REVEL
Benign
0.14
Sift
Benign
0.35
T
Sift4G
Benign
0.47
T
Vest4
0.68
MutPred
0.63
Loss of helix (P = 0.1299);
MVP
0.35
MPC
0.12
ClinPred
0.48
T
GERP RS
4.1
gMVP
0.37

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: rs376991251; hg19: chr3-52381870; API