chr6-38931915-G-A

Variant names:

• chr6-38931915-G-A
• rs112903128
• NM_001206927.2:c.11379G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_001206927.2(DNAH8):​c.11379G>A​(p.Thr3793Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0017 in 1,611,160 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0017 (3 hom.)
• Consequence: DNAH8 NM_001206927.2 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.02
• Publications: 4 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 6-38931915-G-A is Benign according to our data. Variant chr6-38931915-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 238631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-2.02 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.0013 (197/152080) while in subpopulation AMR AF = 0.00242 (37/15272). AF 95% confidence interval is 0.00181. There are 0 homozygotes in GnomAd4. There are 91 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.
• BS2: High Homozygotes in GnomAdExome4 at 3 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.11379G>A	p.Thr3793Thr	synonymous	Exon 76 of 93	NP_001193856.1
	DNAH8	NM_001371.4		c.10728G>A	p.Thr3576Thr	synonymous	Exon 75 of 92	NP_001362.2
	DNAH8-AS1	NR_038401.1		n.160+4378C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH8	ENST00000327475.11	TSL:5 MANE Select	c.11379G>A	p.Thr3793Thr	synonymous	Exon 76 of 93	ENSP00000333363.7
	DNAH8	ENST00000359357.7	TSL:2	c.10728G>A	p.Thr3576Thr	synonymous	Exon 74 of 91	ENSP00000352312.3
	DNAH8	ENST00000449981.6	TSL:5	c.11379G>A	p.Thr3793Thr	synonymous	Exon 75 of 82	ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.00130 AC: 197 AN: 151962 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00243

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000378

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00112 AC: 279 AN: 248068 AF XY: 0.00108

Gnomad AFR exome AF: 0.00112

Gnomad AMR exome AF: 0.000743

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000232

Gnomad NFE exome AF: 0.00197

Gnomad OTH exome AF: 0.00150

GnomAD4 exome AF: 0.00174 AC: 2537 AN: 1459080 Hom.: 3 Cov.: 30 AF XY: 0.00167 AC XY: 1215 AN XY: 725858

African (AFR) AF: 0.000810 AC: 27 AN: 33342

American (AMR) AF: 0.000723 AC: 32 AN: 44282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26082

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.000105 AC: 9 AN: 85738

European-Finnish (FIN) AF: 0.000262 AC: 14 AN: 53376

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00215 AC: 2389 AN: 1110754

Other (OTH) AF: 0.00109 AC: 66 AN: 60278

GnomAD4 genome AF: 0.00130 AC: 197 AN: 152080 Hom.: 0 Cov.: 31 AF XY: 0.00122 AC XY: 91 AN XY: 74350

African (AFR) AF: 0.000723 AC: 30 AN: 41510

American (AMR) AF: 0.00242 AC: 37 AN: 15272

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4806

European-Finnish (FIN) AF: 0.000378 AC: 4 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00185 AC: 126 AN: 67956

Other (OTH) AF: 0.00 AC: 0 AN: 2104

Alfa AF: 0.00164 Hom.: 0

Bravo AF: 0.00133

EpiCase AF: 0.00186

EpiControl AF: 0.00226

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.22
DANN	Benign	0.79
PhyloP100		-2.0
Mutation Taster		=87/13	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: rs112903128; hg19: chr6-38899691; COSMIC: COSV59477697; COSMIC: COSV59477697;