6-38875650-C-T

Variant names:

• chr6-38875650-C-T
• rs6458080
• NM_001206927.2:c.7680C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001206927.2(DNAH8):​c.7680C>T​(p.Val2560Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.447 in 1,611,602 control chromosomes in the GnomAD database, including 167,200 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15226 hom., cov: 32)
  • Exomes 𝑓: 0.45 (151974 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.910
• Publications: 14 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 6-38875650-C-T is Benign according to our data. Variant chr6-38875650-C-T is described in ClinVar as Benign. ClinVar VariationId is 402767.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.91 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.7680C>T	p.Val2560Val	synonymous_variant	Exon 53 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.7680C>T	p.Val2560Val	synonymous_variant	Exon 53 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.7029C>T	p.Val2343Val	synonymous_variant	Exon 51 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.7680C>T	p.Val2560Val	synonymous_variant	Exon 52 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65830 AN: 151828 Hom.: 15187 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.530

Gnomad ASJ AF: 0.360

Gnomad EAS AF: 0.842

Gnomad SAS AF: 0.556

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.395

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.423

GnomAD2 exomes AF: 0.487 AC: 122409 AN: 251178 AF XY: 0.480

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.642

Gnomad ASJ exome AF: 0.365

Gnomad EAS exome AF: 0.847

Gnomad FIN exome AF: 0.372

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.431

GnomAD4 exome AF: 0.448 AC: 654099 AN: 1459654 Hom.: 151974 Cov.: 38 AF XY: 0.448 AC XY: 325708 AN XY: 726256

African (AFR) AF: 0.362 AC: 12089 AN: 33430

American (AMR) AF: 0.628 AC: 28063 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.364 AC: 9498 AN: 26122

East Asian (EAS) AF: 0.821 AC: 32554 AN: 39654

South Asian (SAS) AF: 0.530 AC: 45724 AN: 86210

European-Finnish (FIN) AF: 0.374 AC: 19991 AN: 53386

Middle Eastern (MID) AF: 0.366 AC: 2102 AN: 5748

European-Non Finnish (NFE) AF: 0.429 AC: 476564 AN: 1110096

Other (OTH) AF: 0.456 AC: 27514 AN: 60294

GnomAD4 genome AF: 0.434 AC: 65923 AN: 151948 Hom.: 15226 Cov.: 32 AF XY: 0.436 AC XY: 32355 AN XY: 74248

African (AFR) AF: 0.374 AC: 15479 AN: 41414

American (AMR) AF: 0.531 AC: 8107 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.360 AC: 1247 AN: 3468

East Asian (EAS) AF: 0.842 AC: 4351 AN: 5166

South Asian (SAS) AF: 0.555 AC: 2670 AN: 4810

European-Finnish (FIN) AF: 0.372 AC: 3918 AN: 10540

Middle Eastern (MID) AF: 0.408 AC: 119 AN: 292

European-Non Finnish (NFE) AF: 0.423 AC: 28726 AN: 67976

Other (OTH) AF: 0.428 AC: 904 AN: 2110

Alfa AF: 0.416 Hom.: 6028

Bravo AF: 0.443

Asia WGS AF: 0.679 AC: 2361 AN: 3478

EpiCase AF: 0.421

EpiControl AF: 0.409

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
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.087
DANN	Benign	0.69
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs6458080; hg19: chr6-38843426; COSMIC: COSV59445687;