6-38722852-G-C

Variant names:

• chr6-38722852-G-C
• rs757017842
• NM_001206927.2:c.43G>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.43G>C​(p.Glu15Gln) 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. 13/16 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: 0.717

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]

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=0.11157268).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.43G>C	p.Glu15Gln	missense_variant	Exon 2 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.43G>C	p.Glu15Gln	missense_variant	Exon 2 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000373278.8	c.43G>C	p.Glu15Gln	missense_variant	Exon 2 of 5	1		ENSP00000362375.4
DNAH8	ENST00000449981.6	c.43G>C	p.Glu15Gln	missense_variant	Exon 1 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000417 AC: 1 AN: 239810 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 131636

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000296

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: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000865 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.010	T;.;T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.28	N
LIST_S2	Benign	0.55	T;T;T
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-1.1	T
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.55	.;N;N
REVEL	Benign	0.079
Sift	Benign	0.17	.;T;T
Sift4G	Benign	0.16	.;T;.
Polyphen		0.96	.;D;.
Vest4		0.17
MutPred		0.14		Gain of catalytic residue at E15 (P = 0.1177);Gain of catalytic residue at E15 (P = 0.1177);Gain of catalytic residue at E15 (P = 0.1177);
MVP		0.25
ClinPred		0.94	D
GERP RS		4.5
gMVP		0.15

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: rs757017842; hg19: chr6-38690628;