rs749482996

Positions:

• chr6-38938112-C-G
• chr6-38938112-C-T

Variant summary

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

The NM_001206927.2(DNAH8):​c.11702C>G​(p.Ala3901Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,832 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.830

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 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.11702C>G	p.Ala3901Gly	missense_variant	78/93	ENST00000327475.11	NP_001193856.1
DNAH8-AS1	NR_038401.1	n.61-1720G>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.11702C>G	p.Ala3901Gly	missense_variant	78/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8-AS1	ENST00000416948.1	n.53-1720G>C		intron_variant, non_coding_transcript_variant		2
DNAH8	ENST00000359357.7	c.11051C>G	p.Ala3684Gly	missense_variant	76/91	2		ENSP00000352312	A2
DNAH8	ENST00000449981.6	c.11702C>G	p.Ala3901Gly	missense_variant	77/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000797 AC: 2 AN: 250970 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135638

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000579

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 AF: 0.00000137 AC: 2 AN: 1461832 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 727222

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

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.: 31

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.28	T;T;T
Eigen	Uncertain	0.24
Eigen_PC	Benign	0.20
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D;D;D
M_CAP	Benign	0.040	D
MetaRNN	Uncertain	0.65	D;D;D
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.7	.;.;M
MutationTaster	Benign	0.92	D;D;D
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-3.1	.;D;D
REVEL	Benign	0.24
Sift	Pathogenic	0.0	.;D;D
Polyphen		0.73	.;.;P
Vest4		0.67
MutPred		0.54		.;.;Gain of disorder (P = 0.0883);
MVP		0.64
MPC		0.27
ClinPred		0.98	D
GERP RS		4.7
Varity_R		0.62
gMVP		0.46

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: rs749482996; hg19: chr6-38905888;