rs114095356

chr6-38984223-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001206927.2(DNAH8):c.12969G>A(p.Thr4323=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000503 in 1,592,166 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0023 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.74

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 6-38984223-G-A is Benign according to our data. Variant chr6-38984223-G-A is described in ClinVar as [Benign]. Clinvar id is 414427.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-3.74 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00227 (346/152208) while in subpopulation AFR AF= 0.00742 (308/41510). AF 95% confidence interval is 0.00674. There are 4 homozygotes in gnomad4. There are 161 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.12969G>A	p.Thr4323=	synonymous_variant	87/93	ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.12969G>A	p.Thr4323=	synonymous_variant	87/93	5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.12318G>A	p.Thr4106=	synonymous_variant	85/91	2		A2

Frequencies

GnomAD3 genomes AF: 0.00218 AC: 331 AN: 152088 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00708

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00239

GnomAD3 exomes AF: 0.000760 AC: 190 AN: 249928 Hom.: 1 AF XY: 0.000548 AC XY: 74 AN XY: 135090

Gnomad AFR exome AF: 0.00660

Gnomad AMR exome AF: 0.00146

Gnomad ASJ exome AF: 0.0000996

Gnomad EAS exome AF: 0.0000546

Gnomad SAS exome AF: 0.000297

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000124

Gnomad OTH exome AF: 0.00132

GnomAD4 exome AF: 0.000316 AC: 455 AN: 1439958 Hom.: 0 Cov.: 27 AF XY: 0.000322 AC XY: 231 AN XY: 717554

Gnomad4 AFR exome AF: 0.00769

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.0000385

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000175

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000705

Gnomad4 OTH exome AF: 0.000553

GnomAD4 genome AF: 0.00227 AC: 346 AN: 152208 Hom.: 4 Cov.: 32 AF XY: 0.00216 AC XY: 161 AN XY: 74408

Gnomad4 AFR AF: 0.00742

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00236

Alfa AF: 0.00112 Hom.: 0

Bravo AF: 0.00261

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 21, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
Cadd	Benign	0.023
Dann	Benign	0.46

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: rs114095356; hg19: chr6-38951999; COSMIC: COSV100545982;