chr6-38805517-G-A

Position:

• chr6-38805517-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):​c.3071G>A​(p.Gly1024Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 1,602,908 control chromosomes in the GnomAD database, including 162,349 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13958 hom., cov: 32)
  • Exomes 𝑓: 0.45 (148391 hom.)
• Consequence: DNAH8 NM_001206927.2 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.12

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=5.7039574E-6).
• BP6: Variant 6-38805517-G-A is Benign according to our data. Variant chr6-38805517-G-A is described in ClinVar as [Benign]. Clinvar id is 402762.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.679 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.3071G>A	p.Gly1024Glu	missense_variant	23/93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.3071G>A	p.Gly1024Glu	missense_variant	23/93	5	NM_001206927.2	ENSP00000333363	P2
DNAH8	ENST00000359357.7	c.2420G>A	p.Gly807Glu	missense_variant	21/91	2		ENSP00000352312	A2
DNAH8	ENST00000449981.6	c.3071G>A	p.Gly1024Glu	missense_variant	22/82	5		ENSP00000415331

Frequencies

GnomAD3 genomes AF: 0.416 AC: 63263 AN: 151900 Hom.: 13924 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.337

Gnomad EAS AF: 0.697

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.391

GnomAD3 exomes AF: 0.467 AC: 117096 AN: 250718 Hom.: 29114 AF XY: 0.458 AC XY: 62041 AN XY: 135550

Gnomad AFR exome AF: 0.334

Gnomad AMR exome AF: 0.636

Gnomad ASJ exome AF: 0.341

Gnomad EAS exome AF: 0.717

Gnomad SAS exome AF: 0.448

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.432

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.446 AC: 647553 AN: 1450890 Hom.: 148391 Cov.: 29 AF XY: 0.444 AC XY: 320871 AN XY: 722354

Gnomad4 AFR exome AF: 0.332

Gnomad4 AMR exome AF: 0.623

Gnomad4 ASJ exome AF: 0.344

Gnomad4 EAS exome AF: 0.698

Gnomad4 SAS exome AF: 0.444

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.441

Gnomad4 OTH exome AF: 0.437

GnomAD4 genome AF: 0.417 AC: 63342 AN: 152018 Hom.: 13958 Cov.: 32 AF XY: 0.417 AC XY: 30960 AN XY: 74314

Gnomad4 AFR AF: 0.333

Gnomad4 AMR AF: 0.512

Gnomad4 ASJ AF: 0.337

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.460

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.396

Alfa AF: 0.432 Hom.: 35880

Bravo AF: 0.426

TwinsUK AF: 0.437 AC: 1621

ALSPAC AF: 0.447 AC: 1723

ESP6500AA AF: 0.339 AC: 1492

ESP6500EA AF: 0.438 AC: 3768

ExAC AF: 0.459 AC: 55666

Asia WGS AF: 0.569 AC: 1978 AN: 3470

EpiCase AF: 0.426

EpiControl AF: 0.415

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.78	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	17
DANN	Benign	0.76
DEOGEN2	Benign	0.0065	T;T;T
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.058	N
LIST_S2	Benign	0.11	T;T;T
MetaRNN	Benign	0.0000057	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-0.69	.;.;N
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.41	T
PROVEAN	Benign	1.1	.;N;N
REVEL	Benign	0.057
Sift	Benign	1.0	.;T;T
Polyphen		0.0	.;.;B
Vest4		0.064
MPC		0.16
ClinPred		0.0033	T
GERP RS		4.2
Varity_R		0.031
gMVP		0.16

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: rs874808; hg19: chr6-38773293; COSMIC: COSV59433765;