rs1445823

Positions:

• chr5-13900236-A-C
• chr5-13900236-A-G
• chr5-13900236-A-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001369.3(DNAH5):​c.2229T>G​(p.Asp743Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. D743D) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: DNAH5 NM_001369.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0730

Genes affected

DNAH5 (HGNC:2950): (dynein axonemal heavy chain 5) This gene encodes a dynein protein, which is part of a microtubule-associated motor protein complex consisting of heavy, light, and intermediate chains. This protein is an axonemal heavy chain dynein. It functions as a force-generating protein with ATPase activity, whereby the release of ADP is thought to produce the force-producing power stroke. Mutations in this gene cause primary ciliary dyskinesia type 3, as well as Kartagener syndrome, which are both diseases due to ciliary defects. [provided by RefSeq, Oct 2009]

ENSG00000251423 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05300191).
• BP6: Variant 5-13900236-A-C is Benign according to our data. Variant chr5-13900236-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 258010.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH5	NM_001369.3	c.2229T>G	p.Asp743Glu	missense_variant	15/79	ENST00000265104.5	NP_001360.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH5	ENST00000265104.5	c.2229T>G	p.Asp743Glu	missense_variant	15/79	1	NM_001369.3	ENSP00000265104.4
DNAH5	ENST00000681290.1	c.2184T>G	p.Asp728Glu	missense_variant	15/79			ENSP00000505288.1
ENSG00000251423	ENST00000503244.2	n.3112A>C		non_coding_transcript_exon_variant	3/3	4
ENSG00000251423	ENST00000637153.1	n.3072A>C		non_coding_transcript_exon_variant	3/3	5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 152036 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome Cov.: 42

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 152036 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74260

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

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: 0.00

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.32	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.9
DANN	Benign	0.65
DEOGEN2	Benign	0.040	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.086	N
LIST_S2	Benign	0.41	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.053	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.87	L
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.048
Sift	Benign	0.69	T
Polyphen		0.0	B
Vest4		0.093
MutPred		0.40		Gain of methylation at K746 (P = 0.083);
MVP		0.25
MPC		0.088
ClinPred		0.043	T
GERP RS		-7.2
Varity_R		0.063
gMVP		0.14

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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

Other links and lift over

dbSNP: rs1445823; hg19: chr5-13900345;