6-38775909-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001206927.2(DNAH8):c.1920C>T(p.Asp640=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00395 in 1,612,848 control chromosomes in the GnomAD database, including 201 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (124 hom., cov: 32)
  • Exomes 𝑓: 0.0021 (77 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.421

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-38775909-C-T is Benign according to our data. Variant chr6-38775909-C-T is described in ClinVar as [Benign]. Clinvar id is 414410.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.421 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.1920C>T	p.Asp640=	synonymous_variant	13/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.1920C>T	p.Asp640=	synonymous_variant	13/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.1269C>T	p.Asp423=	synonymous_variant	11/91	2		A2
DNAH8	ENST00000449981.6	c.1920C>T	p.Asp640=	synonymous_variant	12/82	5

Frequencies

GnomAD3 genomes AF: 0.0213 AC: 3243 AN: 152114 Hom.: 122 Cov.: 32

Gnomad AFR AF: 0.0735

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00884

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0149

GnomAD3 exomes AF: 0.00541 AC: 1358 AN: 250912 Hom.: 38 AF XY: 0.00392 AC XY: 532 AN XY: 135762

Gnomad AFR exome AF: 0.0701

Gnomad AMR exome AF: 0.00486

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000449

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.00213 AC: 3111 AN: 1460616 Hom.: 77 Cov.: 29 AF XY: 0.00189 AC XY: 1371 AN XY: 726692

Gnomad4 AFR exome AF: 0.0699

Gnomad4 AMR exome AF: 0.00523

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000928

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000199

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.0214 AC: 3256 AN: 152232 Hom.: 124 Cov.: 32 AF XY: 0.0208 AC XY: 1548 AN XY: 74440

Gnomad4 AFR AF: 0.0736

Gnomad4 AMR AF: 0.00883

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.0147

Alfa AF: 0.00748 Hom.: 21

Bravo AF: 0.0234

Asia WGS AF: 0.00462 AC: 16 AN: 3474

EpiCase AF: 0.000436

EpiControl AF: 0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

May 06, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	2.1
Dann	Benign	0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs78139815; hg19: chr6-38743685;