rs4714192

chr6-38883893-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001206927.2(DNAH8):c.8154C>T(p.Tyr2718=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 1,580,476 control chromosomes in the GnomAD database, including 46,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (3799 hom., cov: 32)
  • Exomes 𝑓: 0.24 (42812 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.322

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 6-38883893-C-T is Benign according to our data. Variant chr6-38883893-C-T is described in ClinVar as [Benign]. Clinvar id is 402768.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.322 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.8154C>T	p.Tyr2718=	synonymous_variant	56/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.8154C>T	p.Tyr2718=	synonymous_variant	56/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.7503C>T	p.Tyr2501=	synonymous_variant	54/91	2		A2
DNAH8	ENST00000449981.6	c.8154C>T	p.Tyr2718=	synonymous_variant	55/82	5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32537 AN: 151776 Hom.: 3793 Cov.: 32

Gnomad AFR AF: 0.152

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.331

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.237

Gnomad OTH AF: 0.212

GnomAD3 exomes AF: 0.244 AC: 58462 AN: 239342 Hom.: 7577 AF XY: 0.247 AC XY: 32029 AN XY: 129880

Gnomad AFR exome AF: 0.144

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.178

Gnomad EAS exome AF: 0.366

Gnomad SAS exome AF: 0.320

Gnomad FIN exome AF: 0.197

Gnomad NFE exome AF: 0.237

Gnomad OTH exome AF: 0.207

GnomAD4 exome AF: 0.241 AC: 344341 AN: 1428580 Hom.: 42812 Cov.: 31 AF XY: 0.243 AC XY: 172548 AN XY: 710252

Gnomad4 AFR exome AF: 0.141

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.326

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.197

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.235

GnomAD4 genome AF: 0.214 AC: 32558 AN: 151896 Hom.: 3799 Cov.: 32 AF XY: 0.215 AC XY: 15949 AN XY: 74196

Gnomad4 AFR AF: 0.152

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.331

Gnomad4 FIN AF: 0.203

Gnomad4 NFE AF: 0.237

Gnomad4 OTH AF: 0.211

Alfa AF: 0.226 Hom.: 8066

Bravo AF: 0.210

Asia WGS AF: 0.305 AC: 1055 AN: 3454

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

Invitae

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
BayesDel_noAF	Benign	-0.37
Cadd	Benign	0.50
Dann	Benign	0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs4714192; hg19: chr6-38851669; COSMIC: COSV59433382;