rs61748646

chr6-38935645-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001206927.2(DNAH8):c.11511G>A(p.Arg3837=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0281 in 1,612,796 control chromosomes in the GnomAD database, including 740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.022 (52 hom., cov: 32)
  • Exomes 𝑓: 0.029 (688 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.30

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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 6-38935645-G-A is Benign according to our data. Variant chr6-38935645-G-A is described in ClinVar as [Benign]. Clinvar id is 257627.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.3 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0219 (3339/152240) while in subpopulation NFE AF= 0.0322 (2188/68026). AF 95% confidence interval is 0.031. There are 52 homozygotes in gnomad4. There are 1660 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.11511G>A	p.Arg3837=	synonymous_variant	77/93	ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.160+648C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.11511G>A	p.Arg3837=	synonymous_variant	77/93	5	NM_001206927.2	P2
DNAH8-AS1	ENST00000416948.1	n.152+648C>T		intron_variant, non_coding_transcript_variant		2
DNAH8	ENST00000359357.7	c.10860G>A	p.Arg3620=	synonymous_variant	75/91	2		A2
DNAH8	ENST00000449981.6	c.11511G>A	p.Arg3837=	synonymous_variant	76/82	5

Frequencies

GnomAD3 genomes AF: 0.0220 AC: 3343 AN: 152122 Hom.: 52 Cov.: 32

Gnomad AFR AF: 0.00459

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0155

Gnomad ASJ AF: 0.0358

Gnomad EAS AF: 0.00577

Gnomad SAS AF: 0.00851

Gnomad FIN AF: 0.0438

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0322

Gnomad OTH AF: 0.0254

GnomAD3 exomes AF: 0.0234 AC: 5872 AN: 250702 Hom.: 97 AF XY: 0.0239 AC XY: 3235 AN XY: 135514

Gnomad AFR exome AF: 0.00414

Gnomad AMR exome AF: 0.0128

Gnomad ASJ exome AF: 0.0393

Gnomad EAS exome AF: 0.00234

Gnomad SAS exome AF: 0.0104

Gnomad FIN exome AF: 0.0383

Gnomad NFE exome AF: 0.0317

Gnomad OTH exome AF: 0.0298

GnomAD4 exome AF: 0.0288 AC: 42016 AN: 1460556 Hom.: 688 Cov.: 30 AF XY: 0.0287 AC XY: 20856 AN XY: 726602

Gnomad4 AFR exome AF: 0.00404

Gnomad4 AMR exome AF: 0.0128

Gnomad4 ASJ exome AF: 0.0400

Gnomad4 EAS exome AF: 0.0107

Gnomad4 SAS exome AF: 0.0105

Gnomad4 FIN exome AF: 0.0388

Gnomad4 NFE exome AF: 0.0316

Gnomad4 OTH exome AF: 0.0273

GnomAD4 genome AF: 0.0219 AC: 3339 AN: 152240 Hom.: 52 Cov.: 32 AF XY: 0.0223 AC XY: 1660 AN XY: 74420

Gnomad4 AFR AF: 0.00457

Gnomad4 AMR AF: 0.0154

Gnomad4 ASJ AF: 0.0358

Gnomad4 EAS AF: 0.00578

Gnomad4 SAS AF: 0.00810

Gnomad4 FIN AF: 0.0438

Gnomad4 NFE AF: 0.0322

Gnomad4 OTH AF: 0.0251

Alfa AF: 0.0307 Hom.: 21

Bravo AF: 0.0183

Asia WGS AF: 0.00491 AC: 17 AN: 3476

EpiCase AF: 0.0298

EpiControl AF: 0.0294

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	6.7
Dann	Benign	0.71

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: rs61748646; hg19: chr6-38903421;