rs12210777

chr6-39008799-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001206927.2(DNAH8):c.13215-15C>T variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.0720

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
DNAH8	NM_001206927.2	c.13215-15C>T		splice_polypyrimidine_tract_variant, intron_variant		ENST00000327475.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH8	ENST00000327475.11	c.13215-15C>T		splice_polypyrimidine_tract_variant, intron_variant		5	NM_001206927.2	P2
DNAH8	ENST00000359357.7	c.12564-15C>T		splice_polypyrimidine_tract_variant, intron_variant		2		A2

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

GnomAD3 exomes AF: 0.127 AC: 30899 AN: 243844 Hom.: 2572 AF XY: 0.123 AC XY: 16222 AN XY: 131700

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 SAS exome AF: 0.154

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

Gnomad4 AFR exome AF: 0.109

Gnomad4 AMR exome AF: 0.247

Gnomad4 ASJ exome AF: 0.111

Gnomad4 EAS exome AF: 0.183

Gnomad4 SAS exome AF: 0.155

Gnomad4 FIN exome AF: 0.0932

Gnomad4 NFE exome AF: 0.0774

Gnomad4 OTH exome AF: 0.0939

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

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.196

Gnomad4 ASJ AF: 0.106

Gnomad4 EAS AF: 0.179

Gnomad4 SAS AF: 0.158

Gnomad4 FIN AF: 0.0959

Gnomad4 NFE AF: 0.0843

Gnomad4 OTH AF: 0.110

Alfa AF: 0.0930 Hom.: 1113

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

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

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

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	7.2
Dann	Benign	0.45

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