rs115871283

chr6-38938834-A-G

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.11853A>G(p.Thr3951=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000448 in 1,612,022 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0024 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00024 (3 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.425

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-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 6-38938834-A-G is Benign according to our data. Variant chr6-38938834-A-G is described in ClinVar as [Benign]. Clinvar id is 414384.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.425 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0024 (366/152334) while in subpopulation AFR AF= 0.00827 (344/41580). AF 95% confidence interval is 0.00755. There are 2 homozygotes in gnomad4. There are 172 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.11853A>G	p.Thr3951=	synonymous_variant	79/93	ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.61-2442T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.11853A>G	p.Thr3951=	synonymous_variant	79/93	5	NM_001206927.2	P2
DNAH8-AS1	ENST00000416948.1	n.53-2442T>C		intron_variant, non_coding_transcript_variant		2
DNAH8	ENST00000359357.7	c.11202A>G	p.Thr3734=	synonymous_variant	77/91	2		A2
DNAH8	ENST00000449981.6	c.11853A>G	p.Thr3951=	synonymous_variant	78/82	5

Frequencies

GnomAD3 genomes AF: 0.00241 AC: 367 AN: 152216 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00832

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

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: 0.0000294

Gnomad OTH AF: 0.000955

GnomAD3 exomes AF: 0.000597 AC: 149 AN: 249426 Hom.: 1 AF XY: 0.000445 AC XY: 60 AN XY: 134824

Gnomad AFR exome AF: 0.00771

Gnomad AMR exome AF: 0.000619

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.000329

GnomAD4 exome AF: 0.000244 AC: 356 AN: 1459688 Hom.: 3 Cov.: 30 AF XY: 0.000201 AC XY: 146 AN XY: 726120

Gnomad4 AFR exome AF: 0.00896

Gnomad4 AMR exome AF: 0.000520

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000810

Gnomad4 OTH exome AF: 0.000415

GnomAD4 genome AF: 0.00240 AC: 366 AN: 152334 Hom.: 2 Cov.: 32 AF XY: 0.00231 AC XY: 172 AN XY: 74492

Gnomad4 AFR AF: 0.00827

Gnomad4 AMR AF: 0.00118

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000879 Hom.: 1

Bravo AF: 0.00271

Asia WGS AF: 0.00115 AC: 4 AN: 3478

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

Nov 19, 2023

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.75
Dann	Benign	0.56

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: rs115871283; hg19: chr6-38906610;