rs61748647

chr6-38951333-C-T

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.12264C>T(p.Asp4088=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00849 in 1,614,020 control chromosomes in the GnomAD database, including 74 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0058 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0088 (71 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00400

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 6-38951333-C-T is Benign according to our data. Variant chr6-38951333-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 238634.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.004 with no splicing effect.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00582 (886/152244) while in subpopulation NFE AF= 0.0102 (692/68028). AF 95% confidence interval is 0.00954. There are 3 homozygotes in gnomad4. There are 406 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.12264C>T	p.Asp4088=	synonymous_variant	82/93	ENST00000327475.11
DNAH8-AS1	NR_038401.1	n.60+1715G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.12264C>T	p.Asp4088=	synonymous_variant	82/93	5	NM_001206927.2	P2
DNAH8-AS1	ENST00000416948.1	n.52+1715G>A		intron_variant, non_coding_transcript_variant		2
DNAH8	ENST00000359357.7	c.11613C>T	p.Asp3871=	synonymous_variant	80/91	2		A2
DNAH8	ENST00000449981.6	c.12264C>T	p.Asp4088=	synonymous_variant	81/82	5

Frequencies

GnomAD3 genomes AF: 0.00582 AC: 886 AN: 152126 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00406

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00387

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0102

Gnomad OTH AF: 0.00431

GnomAD3 exomes AF: 0.00571 AC: 1435 AN: 251408 Hom.: 3 AF XY: 0.00575 AC XY: 781 AN XY: 135878

Gnomad AFR exome AF: 0.00178

Gnomad AMR exome AF: 0.00411

Gnomad ASJ exome AF: 0.000496

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00124

Gnomad FIN exome AF: 0.00388

Gnomad NFE exome AF: 0.00961

Gnomad OTH exome AF: 0.00701

GnomAD4 exome AF: 0.00877 AC: 12819 AN: 1461776 Hom.: 71 Cov.: 31 AF XY: 0.00856 AC XY: 6227 AN XY: 727188

Gnomad4 AFR exome AF: 0.00161

Gnomad4 AMR exome AF: 0.00416

Gnomad4 ASJ exome AF: 0.000459

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.00119

Gnomad4 FIN exome AF: 0.00519

Gnomad4 NFE exome AF: 0.0106

Gnomad4 OTH exome AF: 0.00638

GnomAD4 genome AF: 0.00582 AC: 886 AN: 152244 Hom.: 3 Cov.: 32 AF XY: 0.00545 AC XY: 406 AN XY: 74432

Gnomad4 AFR AF: 0.00181

Gnomad4 AMR AF: 0.00405

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00387

Gnomad4 NFE AF: 0.0102

Gnomad4 OTH AF: 0.00427

Alfa AF: 0.00794 Hom.: 8

Bravo AF: 0.00553

EpiCase AF: 0.00780

EpiControl AF: 0.00966

ClinVar

Significance: Benign/Likely 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 25, 2024

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

DNAH8: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
Cadd	Benign	2.4
Dann	Benign	0.84

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs61748647; hg19: chr6-38919109;