rs111791517

Variant names:

• chr6-38931897-A-G
• rs111791517
• NM_001206927.2:c.11361A>G

Your query was ambiguous. Multiple possible variants found:

• chr6-38931897-A-G
• chr6-38931897-A-T

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.11361A>G​(p.Pro3787Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00382 in 1,612,086 control chromosomes in the GnomAD database, including 89 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.013 (35 hom., cov: 31)
  • Exomes 𝑓: 0.0029 (54 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.244
• 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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 6-38931897-A-G is Benign according to our data. Variant chr6-38931897-A-G is described in ClinVar as Benign. ClinVar VariationId is 414421.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.244 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0128 (1946/152194) while in subpopulation AFR AF = 0.0369 (1532/41518). AF 95% confidence interval is 0.0354. There are 35 homozygotes in GnomAd4. There are 939 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 35 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	NM_001206927.2	MANE Select	c.11361A>G	p.Pro3787Pro	synonymous	Exon 76 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.10710A>G	p.Pro3570Pro	synonymous	Exon 75 of 92	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.160+4396T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11361A>G	p.Pro3787Pro	synonymous	Exon 76 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.10710A>G	p.Pro3570Pro	synonymous	Exon 74 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.11361A>G	p.Pro3787Pro	synonymous	Exon 75 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.0128 AC: 1940 AN: 152076 Hom.: 35 Cov.: 31

Gnomad AFR AF: 0.0368

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0125

Gnomad ASJ AF: 0.0153

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.00194

Gnomad OTH AF: 0.0124

GnomAD2 exomes AF: 0.00504 AC: 1256 AN: 249126 AF XY: 0.00414

Gnomad AFR exome AF: 0.0351

Gnomad AMR exome AF: 0.00813

Gnomad ASJ exome AF: 0.0175

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00175

Gnomad OTH exome AF: 0.00496

GnomAD4 exome AF: 0.00289 AC: 4213 AN: 1459892 Hom.: 54 Cov.: 30 AF XY: 0.00269 AC XY: 1955 AN XY: 726256

African (AFR) AF: 0.0389 AC: 1298 AN: 33362

American (AMR) AF: 0.00812 AC: 361 AN: 44432

Ashkenazi Jewish (ASJ) AF: 0.0166 AC: 434 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39556

South Asian (SAS) AF: 0.000291 AC: 25 AN: 85926

European-Finnish (FIN) AF: 0.0000936 AC: 5 AN: 53400

Middle Eastern (MID) AF: 0.0135 AC: 78 AN: 5758

European-Non Finnish (NFE) AF: 0.00143 AC: 1587 AN: 1111058

Other (OTH) AF: 0.00705 AC: 425 AN: 60300

GnomAD4 genome AF: 0.0128 AC: 1946 AN: 152194 Hom.: 35 Cov.: 31 AF XY: 0.0126 AC XY: 939 AN XY: 74420

African (AFR) AF: 0.0369 AC: 1532 AN: 41518

American (AMR) AF: 0.0124 AC: 190 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0153 AC: 53 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.0000943 AC: 1 AN: 10610

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.00194 AC: 132 AN: 67998

Other (OTH) AF: 0.0123 AC: 26 AN: 2112

Alfa AF: 0.00751 Hom.: 8

Bravo AF: 0.0152

Asia WGS AF: 0.00462 AC: 16 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00267

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	-0.53
CADD	Benign	2.1
DANN	Benign	0.57
PhyloP100		0.24
Mutation Taster		=65/35	polymorphism

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

Other links and lift over

dbSNP: rs111791517; hg19: chr6-38899673;