rs61757623

Variant names:

• chr6-38838025-G-A
• rs61757623
• NM_001206927.2:c.4449G>A

Your query was ambiguous. Multiple possible variants found:

• chr6-38838025-G-A
• chr6-38838025-G-C

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BS1 BS2

The NM_001206927.2(DNAH8):​c.4449G>A​(p.Glu1483Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00105 in 1,608,128 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0057 (4 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (11 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.564
• Publications: 1 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 Gene-Disease associations (from GenCC):

• spermatogenic failure 46

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• spermatogenic failure 5

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 6-38838025-G-A is Benign according to our data. Variant chr6-38838025-G-A is described in ClinVar as Benign. ClinVar VariationId is 414432.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.564 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00572 (871/152204) while in subpopulation AFR AF = 0.0199 (827/41514). AF 95% confidence interval is 0.0188. There are 4 homozygotes in GnomAd4. There are 424 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001206927.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.4449G>A	p.Glu1483Glu	synonymous	Exon 33 of 93	NP_001193856.1	A0A075B6F3
	DNAH8	NM_001371.4		c.3798G>A	p.Glu1266Glu	synonymous	Exon 32 of 92	NP_001362.2	Q96JB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.4449G>A	p.Glu1483Glu	synonymous	Exon 33 of 93	ENSP00000333363.7	A0A075B6F3
	DNAH8	ENST00000359357.7	TSL:2	c.3798G>A	p.Glu1266Glu	synonymous	Exon 31 of 91	ENSP00000352312.3	Q96JB1-1
	DNAH8	ENST00000449981.6	TSL:5	c.4449G>A	p.Glu1483Glu	synonymous	Exon 32 of 82	ENSP00000415331.2	H0Y7V4

Frequencies

GnomAD3 genomes AF: 0.00571 AC: 868 AN: 152086 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.0199

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00151 AC: 374 AN: 246906 AF XY: 0.00111

Gnomad AFR exome AF: 0.0211

Gnomad AMR exome AF: 0.000789

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000444

Gnomad OTH exome AF: 0.000331

GnomAD4 exome AF: 0.000557 AC: 811 AN: 1455924 Hom.: 11 Cov.: 29 AF XY: 0.000498 AC XY: 361 AN XY: 724298

African (AFR) AF: 0.0204 AC: 675 AN: 33154

American (AMR) AF: 0.00111 AC: 48 AN: 43282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25966

East Asian (EAS) AF: 0.00 AC: 0 AN: 39514

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85190

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53342

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5752

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1109526

Other (OTH) AF: 0.00108 AC: 65 AN: 60198

GnomAD4 genome AF: 0.00572 AC: 871 AN: 152204 Hom.: 4 Cov.: 32 AF XY: 0.00570 AC XY: 424 AN XY: 74418

African (AFR) AF: 0.0199 AC: 827 AN: 41514

American (AMR) AF: 0.00190 AC: 29 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68002

Other (OTH) AF: 0.00426 AC: 9 AN: 2114

Alfa AF: 0.00270 Hom.: 3

Bravo AF: 0.00629

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000594

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.0
DANN	Benign	0.41
PhyloP100		0.56
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism

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: rs61757623; hg19: chr6-38805801;