6-38842808-G-C

Position:

• chr6-38842808-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001206927.2(DNAH8):​c.4750G>C​(p.Glu1584Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/20 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: 32)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.24

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18996474).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.4750G>C	p.Glu1584Gln	missense_variant	35/93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.4750G>C	p.Glu1584Gln	missense_variant	35/93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.4099G>C	p.Glu1367Gln	missense_variant	33/91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.4750G>C	p.Glu1584Gln	missense_variant	34/82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;T;T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.061
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Benign	0.73	T;T;T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.19	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	.;.;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.67	.;N;N
REVEL	Benign	0.077
Sift	Benign	0.42	.;T;T
Polyphen		0.011	.;.;B
Vest4		0.29
MutPred		0.36		.;.;Gain of MoRF binding (P = 0.0483);
MVP		0.65
MPC		0.13
ClinPred		0.69	D
GERP RS		5.1
Varity_R		0.17
gMVP		0.31

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

Other links and lift over

dbSNP: rs201823651; hg19: chr6-38810584;