6-38883033-C-G

Position:

• chr6-38883033-C-G

Variant summary

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

The NM_001206927.2(DNAH8):​c.7982C>G​(p.Thr2661Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000692 in 1,444,340 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2661N) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.92

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 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
DNAH8	NM_001206927.2	c.7982C>G	p.Thr2661Ser	missense_variant	54/93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.7982C>G	p.Thr2661Ser	missense_variant	54/93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.7331C>G	p.Thr2444Ser	missense_variant	52/91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.7982C>G	p.Thr2661Ser	missense_variant	53/82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000422 AC: 1 AN: 236978 Hom.: 0 AF XY: 0.00000780 AC XY: 1 AN XY: 128138

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000373

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444340 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 717950

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: 0.0000123

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.067	T;T;T
Eigen	Pathogenic	0.69
Eigen_PC	Pathogenic	0.69
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.69	D;D;D
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	.;.;M
PrimateAI	Uncertain	0.57	T
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Benign	0.27
Sift	Benign	0.037	.;D;T
Polyphen		1.0	.;.;D
Vest4		0.52
MutPred		0.35		.;.;Loss of helix (P = 0.0558);
MVP		0.60
MPC		0.43
ClinPred		0.94	D
GERP RS		5.9
Varity_R		0.42
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: rs862432; hg19: chr6-38850809;