rs76387239

chr6-38913932-G-Achr6-38913932-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001206927.2(DNAH8):c.9943G>A(p.Ala3315Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000584 in 1,612,476 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0031 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00032 (4 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.95

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:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.008771926).
• BP6: Variant 6-38913932-G-A is Benign according to our data. Variant chr6-38913932-G-A is described in ClinVar as [Benign]. Clinvar id is 414418.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00311 (474/152260) while in subpopulation AFR AF= 0.0109 (453/41558). AF 95% confidence interval is 0.0101. There are 4 homozygotes in gnomad4. There are 222 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.9943G>A	p.Ala3315Thr	missense_variant	67/93	ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.783-6095C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.9943G>A	p.Ala3315Thr	missense_variant	67/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.9292G>A	p.Ala3098Thr	missense_variant	65/91	2		A2
DNAH8	ENST00000449981.6	c.9943G>A	p.Ala3315Thr	missense_variant	66/82	5

Frequencies

GnomAD3 genomes AF: 0.00311 AC: 473 AN: 152142 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00334

GnomAD3 exomes AF: 0.000865 AC: 217 AN: 250934 Hom.: 3 AF XY: 0.000612 AC XY: 83 AN XY: 135626

Gnomad AFR exome AF: 0.0124

Gnomad AMR exome AF: 0.000347

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: 0.0000265

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000320 AC: 467 AN: 1460216 Hom.: 4 Cov.: 30 AF XY: 0.000270 AC XY: 196 AN XY: 726234

Gnomad4 AFR exome AF: 0.0114

Gnomad4 AMR exome AF: 0.000537

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000540

Gnomad4 OTH exome AF: 0.000812

GnomAD4 genome AF: 0.00311 AC: 474 AN: 152260 Hom.: 4 Cov.: 33 AF XY: 0.00298 AC XY: 222 AN XY: 74450

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.000357 Hom.: 1

Bravo AF: 0.00359

ESP6500AA AF: 0.00999 AC: 44

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00119 AC: 145

Asia WGS AF: 0.00173 AC: 6 AN: 3478

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.16
Cadd	Benign	22
Dann	Uncertain	1.0
DEOGEN2	Benign	0.11	T;D;T
Eigen	Pathogenic	0.83
Eigen_PC	Pathogenic	0.79
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.89	D;D;D
MetaRNN	Benign	0.0088	T;T;T
MetaSVM	Uncertain	0.0028	D
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.57	T
REVEL	Uncertain	0.62
Polyphen		1.0	.;.;D
Vest4		0.14
MVP		0.76
MPC		0.43
ClinPred		0.067	T
GERP RS		6.1
Varity_R		0.55
gMVP		0.43

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs76387239; hg19: chr6-38881708;