rs4714192

Variant names:

• chr6-38883893-C-T
• rs4714192
• NM_001206927.2:c.8154C>T

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001206927.2(DNAH8):​c.8154C>T​(p.Tyr2718Tyr) 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:4
• Conservation: PhyloP100: -0.322
• Publications: 13 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: ClinGen, Labcorp Genetics (formerly Invitae)
• 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 -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.8154C>T	p.Tyr2718Tyr	synonymous	Exon 56 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.7503C>T	p.Tyr2501Tyr	synonymous	Exon 55 of 92	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.8154C>T	p.Tyr2718Tyr	synonymous	Exon 56 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.7503C>T	p.Tyr2501Tyr	synonymous	Exon 54 of 91	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.8154C>T	p.Tyr2718Tyr	synonymous	Exon 55 of 82	ENSP00000415331.2	H0Y7V4

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

GnomAD2 exomes AF: 0.244 AC: 58462 AN: 239342 AF XY: 0.247

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 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

African (AFR) AF: 0.141 AC: 4574 AN: 32432

American (AMR) AF: 0.238 AC: 10066 AN: 42280

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4415 AN: 25364

East Asian (EAS) AF: 0.326 AC: 12461 AN: 38182

South Asian (SAS) AF: 0.321 AC: 25897 AN: 80712

European-Finnish (FIN) AF: 0.197 AC: 10204 AN: 51892

Middle Eastern (MID) AF: 0.210 AC: 1189 AN: 5654

European-Non Finnish (NFE) AF: 0.239 AC: 261714 AN: 1093320

Other (OTH) AF: 0.235 AC: 13821 AN: 58744

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

African (AFR) AF: 0.152 AC: 6285 AN: 41470

American (AMR) AF: 0.214 AC: 3261 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3470

East Asian (EAS) AF: 0.365 AC: 1878 AN: 5152

South Asian (SAS) AF: 0.331 AC: 1590 AN: 4802

European-Finnish (FIN) AF: 0.203 AC: 2129 AN: 10504

Middle Eastern (MID) AF: 0.243 AC: 71 AN: 292

European-Non Finnish (NFE) AF: 0.237 AC: 16103 AN: 67930

Other (OTH) AF: 0.211 AC: 445 AN: 2110

Alfa AF: 0.226 Hom.: 17180

Bravo AF: 0.210

Asia WGS AF: 0.305 AC: 1055 AN: 3454

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	0.50
DANN	Benign	0.42
PhyloP100		-0.32
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4714192; hg19: chr6-38851669; COSMIC: COSV59433382;