rs200564814

Variant names:

• chr6-38842413-C-T
• rs200564814
• NM_001206927.2:c.4512C>T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2 BP4_Strong BP6_Very_Strong BP7

The NM_001206927.2(DNAH8):​c.4512C>T​(p.Thr1504Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000544 in 1,611,372 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00032 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (1 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.870

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 -11 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 6-38842413-C-T is Benign according to our data. Variant chr6-38842413-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 454572.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.87 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.4512C>T	p.Thr1504Thr	synonymous_variant	Exon 34 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.4512C>T	p.Thr1504Thr	synonymous_variant	Exon 34 of 93	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.3861C>T	p.Thr1287Thr	synonymous_variant	Exon 32 of 91	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.4512C>T	p.Thr1504Thr	synonymous_variant	Exon 33 of 82	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.000316 AC: 48 AN: 151928 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000484

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000786

Gnomad ASJ AF: 0.00230

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000324

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.000372 AC: 93 AN: 250034 Hom.: 0 AF XY: 0.000400 AC XY: 54 AN XY: 135086

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000204

Gnomad ASJ exome AF: 0.00319

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000594

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000292

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000568 AC: 829 AN: 1459444 Hom.: 1 Cov.: 30 AF XY: 0.000552 AC XY: 401 AN XY: 725912

Gnomad4 AFR exome AF: 0.000150

Gnomad4 AMR exome AF: 0.000202

Gnomad4 ASJ exome AF: 0.00330

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000408

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000593

Gnomad4 OTH exome AF: 0.000581

GnomAD4 genome AF: 0.000316 AC: 48 AN: 151928 Hom.: 0 Cov.: 32 AF XY: 0.000364 AC XY: 27 AN XY: 74184

Gnomad4 AFR AF: 0.0000484

Gnomad4 AMR AF: 0.000786

Gnomad4 ASJ AF: 0.00230

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000324

Gnomad4 OTH AF: 0.000959

Alfa AF: 0.000491 Hom.: 1

Bravo AF: 0.000325

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Oct 29, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

DNAH8-related disorder Benign:1

Apr 12, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided Benign:1

May 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH8: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	4.5
DANN	Benign	0.58

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

Publications

LitVar

Other links and lift over

dbSNP: rs200564814; hg19: chr6-38810189;