chr6-38931876-A-G

Variant names:

• chr6-38931876-A-G
• rs113024778
• NM_001206927.2:c.11340A>G

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.11340A>G​(p.Leu3780Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,611,290 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0029 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00027 (2 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: 1.35
• 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-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 6-38931876-A-G is Benign according to our data. Variant chr6-38931876-A-G is described in ClinVar as Benign. ClinVar VariationId is 414405.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.36 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00295 (449/152242) while in subpopulation AFR AF = 0.0104 (430/41532). AF 95% confidence interval is 0.00955. There are 2 homozygotes in GnomAd4. There are 203 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 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.11340A>G	p.Leu3780Leu	synonymous	Exon 76 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.10689A>G	p.Leu3563Leu	synonymous	Exon 75 of 92	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.160+4417T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11340A>G	p.Leu3780Leu	synonymous	Exon 76 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.10689A>G	p.Leu3563Leu	synonymous	Exon 74 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.11340A>G	p.Leu3780Leu	synonymous	Exon 75 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.00294 AC: 448 AN: 152124 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

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: 0.0000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000810 AC: 201 AN: 248284 AF XY: 0.000559

Gnomad AFR exome AF: 0.0117

Gnomad AMR exome AF: 0.000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000178

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000273 AC: 398 AN: 1459048 Hom.: 2 Cov.: 29 AF XY: 0.000225 AC XY: 163 AN XY: 725832

African (AFR) AF: 0.0104 AC: 346 AN: 33330

American (AMR) AF: 0.000429 AC: 19 AN: 44258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26096

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00 AC: 0 AN: 85664

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5758

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1110772

Other (OTH) AF: 0.000481 AC: 29 AN: 60296

GnomAD4 genome AF: 0.00295 AC: 449 AN: 152242 Hom.: 2 Cov.: 32 AF XY: 0.00273 AC XY: 203 AN XY: 74448

African (AFR) AF: 0.0104 AC: 430 AN: 41532

American (AMR) AF: 0.000850 AC: 13 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00189 AC: 4 AN: 2112

Alfa AF: 0.00170 Hom.: 0

Bravo AF: 0.00346

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	DNAH8-related disorder (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	3.6
DANN	Benign	0.75
PhyloP100		1.4
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: rs113024778; hg19: chr6-38899652;