6-38923292-T-G

Variant names:

• chr6-38923292-T-G
• rs4714199
• NM_001206927.2:c.10790+107T>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001206927.2(DNAH8):​c.10790+107T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 1,362,986 control chromosomes in the GnomAD database, including 17,879 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.22 (5638 hom., cov: 32)
  • Exomes 𝑓: 0.13 (12241 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.224

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

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 6-38923292-T-G is Benign according to our data. Variant chr6-38923292-T-G is described in ClinVar as [Benign]. Clinvar id is 1224224.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.10790+107T>G		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+107T>G		intron_variant	Intron 72 of 92	5	NM_001206927.2	ENSP00000333363.7

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32930 AN: 152032 Hom.: 5624 Cov.: 32

Gnomad AFR AF: 0.471

Gnomad AMI AF: 0.116

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.0745

Gnomad FIN AF: 0.104

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.184

GnomAD4 exome AF: 0.125 AC: 151805 AN: 1210836 Hom.: 12241 Cov.: 15 AF XY: 0.123 AC XY: 73725 AN XY: 601714

Gnomad4 AFR exome AF: 0.478

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.275

Gnomad4 SAS exome AF: 0.0667

Gnomad4 FIN exome AF: 0.104

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.217 AC: 32976 AN: 152150 Hom.: 5638 Cov.: 32 AF XY: 0.211 AC XY: 15694 AN XY: 74376

Gnomad4 AFR AF: 0.471

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.0735

Gnomad4 FIN AF: 0.104

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.182

Alfa AF: 0.120 Hom.: 2823

Bravo AF: 0.235

Asia WGS AF: 0.183 AC: 636 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 11, 2018

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	-0.83
CADD	Benign	2.4
DANN	Benign	0.79

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

Publications

LitVar

Other links and lift over

dbSNP: rs4714199; hg19: chr6-38891068; COSMIC: COSV59422084; COSMIC: COSV59422084;