6-38890771-G-T

Variant names:

• chr6-38890771-G-T
• rs146573461
• NM_001206927.2:c.8583+10G>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS1

The NM_001206927.2(DNAH8):​c.8583+10G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00068 in 1,586,078 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00041 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00071 (0 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.734
• 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 Gene-Disease associations (from GenCC):

• spermatogenic failure 46

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen
• spermatogenic failure 5

  Inheritance: AR Classification: MODERATE Submitted by: Franklin by Genoox
• primary ciliary dyskinesia

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 6-38890771-G-T is Benign according to our data. Variant chr6-38890771-G-T is described in ClinVar as Likely_benign. ClinVar VariationId is 454604.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAdExome4 allele frequency = 0.000709 (1017/1433908) while in subpopulation NFE AF = 0.000903 (981/1086846). AF 95% confidence interval is 0.000855. There are 0 homozygotes in GnomAdExome4. There are 467 alleles in the male GnomAdExome4 subpopulation. Median coverage is 25. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.8583+10G>T		intron_variant	Intron 58 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.8583+10G>T		intron_variant	Intron 58 of 92	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.7932+10G>T		intron_variant	Intron 56 of 90	2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.8583+10G>T		intron_variant	Intron 57 of 81	5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.000401 AC: 61 AN: 152052 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000260 AC: 65 AN: 250150 AF XY: 0.000244

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.0000582

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000530

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000709 AC: 1017 AN: 1433908 Hom.: 0 Cov.: 25 AF XY: 0.000653 AC XY: 467 AN XY: 715174

African (AFR) AF: 0.0000608 AC: 2 AN: 32904

American (AMR) AF: 0.0000896 AC: 4 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25922

East Asian (EAS) AF: 0.00 AC: 0 AN: 39508

South Asian (SAS) AF: 0.00 AC: 0 AN: 85536

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.000903 AC: 981 AN: 1086846

Other (OTH) AF: 0.000505 AC: 30 AN: 59436

GnomAD4 genome AF: 0.000407 AC: 62 AN: 152170 Hom.: 0 Cov.: 32 AF XY: 0.000323 AC XY: 24 AN XY: 74382

African (AFR) AF: 0.000289 AC: 12 AN: 41516

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

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

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10584

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

European-Non Finnish (NFE) AF: 0.000721 AC: 49 AN: 68000

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.000277 Hom.: 0

Bravo AF: 0.000351

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Sep 22, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

DNAH8-related disorder Benign:1

Mar 04, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	7.2
DANN	Benign	0.72
PhyloP100		-0.73
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: rs146573461; hg19: chr6-38858547;