rs78611987

Variant names:

• chr6-38873307-T-C
• rs78611987
• NM_001206927.2:c.7551T>C

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.7551T>C​(p.Asp2517Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0112 in 1,613,678 control chromosomes in the GnomAD database, including 903 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.011 (88 hom., cov: 32)
  • Exomes 𝑓: 0.011 (815 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0380
• Publications: 5 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=-0.84).
• BP6: Variant 6-38873307-T-C is Benign according to our data. Variant chr6-38873307-T-C is described in ClinVar as Benign. ClinVar VariationId is 414422.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.038 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.7551T>C	p.Asp2517Asp	synonymous_variant	Exon 52 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.7551T>C	p.Asp2517Asp	synonymous_variant	Exon 52 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.6900T>C	p.Asp2300Asp	synonymous_variant	Exon 50 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.7551T>C	p.Asp2517Asp	synonymous_variant	Exon 51 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.0110 AC: 1679 AN: 152198 Hom.: 89 Cov.: 32

Gnomad AFR AF: 0.00446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00746

Gnomad ASJ AF: 0.00490

Gnomad EAS AF: 0.147

Gnomad SAS AF: 0.0969

Gnomad FIN AF: 0.000376

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00162

Gnomad OTH AF: 0.00813

GnomAD2 exomes AF: 0.0248 AC: 6194 AN: 249650 AF XY: 0.0277

Gnomad AFR exome AF: 0.00359

Gnomad AMR exome AF: 0.0153

Gnomad ASJ exome AF: 0.00429

Gnomad EAS exome AF: 0.141

Gnomad FIN exome AF: 0.000694

Gnomad NFE exome AF: 0.00172

Gnomad OTH exome AF: 0.0148

GnomAD4 exome AF: 0.0112 AC: 16411 AN: 1461362 Hom.: 815 Cov.: 34 AF XY: 0.0136 AC XY: 9892 AN XY: 726948

African (AFR) AF: 0.00400 AC: 134 AN: 33466

American (AMR) AF: 0.0139 AC: 623 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.00448 AC: 117 AN: 26122

East Asian (EAS) AF: 0.134 AC: 5334 AN: 39660

South Asian (SAS) AF: 0.0882 AC: 7587 AN: 86056

European-Finnish (FIN) AF: 0.000749 AC: 40 AN: 53382

Middle Eastern (MID) AF: 0.0140 AC: 81 AN: 5766

European-Non Finnish (NFE) AF: 0.00132 AC: 1467 AN: 1111848

Other (OTH) AF: 0.0170 AC: 1028 AN: 60390

GnomAD4 genome AF: 0.0110 AC: 1675 AN: 152316 Hom.: 88 Cov.: 32 AF XY: 0.0134 AC XY: 998 AN XY: 74474

African (AFR) AF: 0.00455 AC: 189 AN: 41568

American (AMR) AF: 0.00745 AC: 114 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00490 AC: 17 AN: 3468

East Asian (EAS) AF: 0.147 AC: 759 AN: 5178

South Asian (SAS) AF: 0.0962 AC: 464 AN: 4824

European-Finnish (FIN) AF: 0.000376 AC: 4 AN: 10628

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00162 AC: 110 AN: 68028

Other (OTH) AF: 0.00804 AC: 17 AN: 2114

Alfa AF: 0.00337 Hom.: 5

Bravo AF: 0.0102

Asia WGS AF: 0.105 AC: 362 AN: 3476

EpiCase AF: 0.00267

EpiControl AF: 0.00285

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 04, 2021

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	-0.84
CADD	Benign	1.0
DANN	Benign	0.39
PhyloP100		-0.038
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: rs78611987; hg19: chr6-38841083; COSMIC: COSV59438757; COSMIC: COSV59438757;