6-39008799-C-T

Variant names:

• chr6-39008799-C-T
• rs12210777
• NM_001206927.2:c.13215-15C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):​c.13215-15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0944 in 1,552,822 control chromosomes in the GnomAD database, including 8,431 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1085 hom., cov: 30)
  • Exomes 𝑓: 0.093 (7346 hom.)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0720
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 6-39008799-C-T is Benign according to our data. Variant chr6-39008799-C-T is described in ClinVar as Benign. ClinVar VariationId is 402770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.13215-15C>T		intron_variant	Intron 88 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.13215-15C>T		intron_variant	Intron 88 of 92	5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.12564-15C>T		intron_variant	Intron 86 of 90	2		ENSP00000352312.3

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16524 AN: 151370 Hom.: 1081 Cov.: 30

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.196

Gnomad ASJ AF: 0.106

Gnomad EAS AF: 0.179

Gnomad SAS AF: 0.159

Gnomad FIN AF: 0.0959

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0843

Gnomad OTH AF: 0.106

GnomAD2 exomes AF: 0.127 AC: 30899 AN: 243844 AF XY: 0.123

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.260

Gnomad ASJ exome AF: 0.106

Gnomad EAS exome AF: 0.168

Gnomad FIN exome AF: 0.0953

Gnomad NFE exome AF: 0.0847

Gnomad OTH exome AF: 0.112

GnomAD4 exome AF: 0.0928 AC: 130026 AN: 1401338 Hom.: 7346 Cov.: 25 AF XY: 0.0946 AC XY: 66162 AN XY: 699516

African (AFR) AF: 0.109 AC: 3489 AN: 32094

American (AMR) AF: 0.247 AC: 10616 AN: 43058

Ashkenazi Jewish (ASJ) AF: 0.111 AC: 2788 AN: 25224

East Asian (EAS) AF: 0.183 AC: 7185 AN: 39166

South Asian (SAS) AF: 0.155 AC: 12715 AN: 82260

European-Finnish (FIN) AF: 0.0932 AC: 4934 AN: 52918

Middle Eastern (MID) AF: 0.0994 AC: 557 AN: 5606

European-Non Finnish (NFE) AF: 0.0774 AC: 82274 AN: 1062764

Other (OTH) AF: 0.0939 AC: 5468 AN: 58248

GnomAD4 genome AF: 0.109 AC: 16546 AN: 151484 Hom.: 1085 Cov.: 30 AF XY: 0.113 AC XY: 8363 AN XY: 73946

African (AFR) AF: 0.109 AC: 4496 AN: 41312

American (AMR) AF: 0.196 AC: 2976 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 367 AN: 3472

East Asian (EAS) AF: 0.179 AC: 917 AN: 5116

South Asian (SAS) AF: 0.158 AC: 755 AN: 4782

European-Finnish (FIN) AF: 0.0959 AC: 996 AN: 10384

Middle Eastern (MID) AF: 0.0993 AC: 29 AN: 292

European-Non Finnish (NFE) AF: 0.0843 AC: 5727 AN: 67928

Other (OTH) AF: 0.110 AC: 231 AN: 2096

Alfa AF: 0.0939 Hom.: 1689

Bravo AF: 0.115

Asia WGS AF: 0.165 AC: 573 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

May 12, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.2
DANN	Benign	0.45
PhyloP100		0.072
Mutation Taster		=100/0	polymorphism (auto)

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: rs12210777; hg19: chr6-38976575; COSMIC: COSV59450762;