chr6-38805517-G-A

Variant names:

• chr6-38805517-G-A
• rs874808
• NM_001206927.2:c.3071G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/20 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
• Publications: 21 publications found

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 Gene-Disease associations (from GenCC):

• spermatogenic failure 46

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• spermatogenic failure 5

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.3071G>A	p.Gly1024Glu	missense_variant	Exon 23 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.3071G>A	p.Gly1024Glu	missense_variant	Exon 23 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.2420G>A	p.Gly807Glu	missense_variant	Exon 21 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.3071G>A	p.Gly1024Glu	missense_variant	Exon 22 of 82	5		ENSP00000415331.2

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

GnomAD2 exomes AF: 0.467 AC: 117096 AN: 250718 AF XY: 0.458

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 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

African (AFR) AF: 0.332 AC: 11029 AN: 33268

American (AMR) AF: 0.623 AC: 27752 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.344 AC: 8956 AN: 26056

East Asian (EAS) AF: 0.698 AC: 27549 AN: 39486

South Asian (SAS) AF: 0.444 AC: 38145 AN: 85958

European-Finnish (FIN) AF: 0.377 AC: 20075 AN: 53270

Middle Eastern (MID) AF: 0.351 AC: 2017 AN: 5744

European-Non Finnish (NFE) AF: 0.441 AC: 485778 AN: 1102552

Other (OTH) AF: 0.437 AC: 26252 AN: 60008

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

African (AFR) AF: 0.333 AC: 13821 AN: 41470

American (AMR) AF: 0.512 AC: 7825 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.337 AC: 1169 AN: 3466

East Asian (EAS) AF: 0.698 AC: 3615 AN: 5180

South Asian (SAS) AF: 0.460 AC: 2213 AN: 4816

European-Finnish (FIN) AF: 0.372 AC: 3925 AN: 10552

Middle Eastern (MID) AF: 0.401 AC: 118 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29330 AN: 67934

Other (OTH) AF: 0.396 AC: 838 AN: 2114

Alfa AF: 0.429 Hom.: 49169

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

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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
PhyloP100		2.1
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
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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