6-38923310-A-C

Variant names:

• chr6-38923310-A-C
• rs115503147
• NM_001206927.2:c.10790+125A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001206927.2(DNAH8):​c.10790+125A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00349 in 1,151,216 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (65 hom., cov: 32)
  • Exomes 𝑓: 0.0016 (38 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.85
• Publications: 0 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 6-38923310-A-C is Benign according to our data. Variant chr6-38923310-A-C is described in ClinVar as [Benign]. Clinvar id is 1238648.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.052 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.10790+125A>C		intron_variant	Intron 72 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.10790+125A>C		intron_variant	Intron 72 of 92	5	NM_001206927.2	ENSP00000333363.7

Frequencies

GnomAD3 genomes AF: 0.0156 AC: 2368 AN: 152074 Hom.: 65 Cov.: 32

Gnomad AFR AF: 0.0540

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000397

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.00164 AC: 1641 AN: 999024 Hom.: 38 Cov.: 12 AF XY: 0.00155 AC XY: 777 AN XY: 501566

African (AFR) AF: 0.0522 AC: 1173 AN: 22490

American (AMR) AF: 0.00392 AC: 94 AN: 23960

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17492

East Asian (EAS) AF: 0.00 AC: 0 AN: 34568

South Asian (SAS) AF: 0.0000513 AC: 3 AN: 58460

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36924

Middle Eastern (MID) AF: 0.00333 AC: 11 AN: 3308

European-Non Finnish (NFE) AF: 0.000277 AC: 210 AN: 757922

Other (OTH) AF: 0.00342 AC: 150 AN: 43900

GnomAD4 genome AF: 0.0156 AC: 2372 AN: 152192 Hom.: 65 Cov.: 32 AF XY: 0.0149 AC XY: 1109 AN XY: 74398

African (AFR) AF: 0.0539 AC: 2236 AN: 41492

American (AMR) AF: 0.00543 AC: 83 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000397 AC: 27 AN: 68028

Other (OTH) AF: 0.0109 AC: 23 AN: 2114

Alfa AF: 0.0134 Hom.: 6

Bravo AF: 0.0171

Asia WGS AF: 0.00375 AC: 13 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

May 24, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.11
DANN	Benign	0.51
PhyloP100		-1.8
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: rs115503147; hg19: chr6-38891086;