rs760781678

Variant names:

• chr6-38935665-A-G
• NM_001206927.2:c.11531A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-38935665-A-G
• chr6-38935665-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001206927.2(DNAH8):​c.11531A>G​(p.Asp3844Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.18

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-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.11531A>G	p.Asp3844Gly	missense_variant	Exon 77 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.11531A>G	p.Asp3844Gly	missense_variant	Exon 77 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.10880A>G	p.Asp3627Gly	missense_variant	Exon 75 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.11531A>G	p.Asp3844Gly	missense_variant	Exon 76 of 82	5		ENSP00000415331.2
DNAH8-AS1	ENST00000416948.1	n.152+628T>C		intron_variant	Intron 2 of 3	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460616 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 726642

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Pathogenic	0.14
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.30	T;T;T
Eigen	Pathogenic	0.99
Eigen_PC	Pathogenic	0.93
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.033	D
MetaRNN	Pathogenic	0.85	D;D;D
MetaSVM	Uncertain	-0.26	T
MutationAssessor	Pathogenic	3.9	.;.;H
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-6.6	.;D;D
REVEL	Uncertain	0.51
Sift	Benign	0.11	.;T;T
Polyphen		1.0	.;.;D
Vest4		0.94
MutPred		0.56		.;.;Loss of stability (P = 0.0345);
MVP		0.77
MPC		0.64
ClinPred		1.0	D
GERP RS		6.0
Varity_R		0.62
gMVP		0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.94		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.94		Position offset: -1
DS_DL_spliceai		0.71		Position offset: 32

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-38903441;