rs61748646

Variant names:

• chr6-38935645-G-A
• rs61748646
• NM_001206927.2:c.11511G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001206927.2(DNAH8):​c.11511G>A​(p.Arg3837Arg) 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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 52 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.11511G>A	p.Arg3837Arg	synonymous_variant	Exon 77 of 93	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.11511G>A	p.Arg3837Arg	synonymous_variant	Exon 77 of 93	5	NM_001206927.2	ENSP00000333363.7

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

GnomAD2 exomes AF: 0.0234 AC: 5872 AN: 250702 AF XY: 0.0239

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 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

African (AFR) AF: 0.00404 AC: 135 AN: 33444

American (AMR) AF: 0.0128 AC: 572 AN: 44672

Ashkenazi Jewish (ASJ) AF: 0.0400 AC: 1044 AN: 26094

East Asian (EAS) AF: 0.0107 AC: 425 AN: 39596

South Asian (SAS) AF: 0.0105 AC: 905 AN: 86174

European-Finnish (FIN) AF: 0.0388 AC: 2064 AN: 53212

Middle Eastern (MID) AF: 0.0208 AC: 120 AN: 5758

European-Non Finnish (NFE) AF: 0.0316 AC: 35105 AN: 1111256

Other (OTH) AF: 0.0273 AC: 1646 AN: 60350

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

African (AFR) AF: 0.00457 AC: 190 AN: 41548

American (AMR) AF: 0.0154 AC: 235 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0358 AC: 124 AN: 3466

East Asian (EAS) AF: 0.00578 AC: 30 AN: 5188

South Asian (SAS) AF: 0.00810 AC: 39 AN: 4816

European-Finnish (FIN) AF: 0.0438 AC: 464 AN: 10594

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0322 AC: 2188 AN: 68026

Other (OTH) AF: 0.0251 AC: 53 AN: 2112

Alfa AF: 0.0304 Hom.: 35

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

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.38
CADD	Benign	6.7
DANN	Benign	0.71
PhyloP100		1.3
Mutation Taster		=97/3	polymorphism (auto)

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

Other links and lift over

dbSNP: rs61748646; hg19: chr6-38903421;