chr2-84528872-A-ATTTT

Variant names:

• chr2-84528872-A-ATTTT
• rs67469465
• NM_001370.2:c.400-24_400-21dupTTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001370.2(DNAH6):​c.400-24_400-21dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000587 in 1,328,166 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.00010 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00065 (0 hom.)
• Consequence: DNAH6 NM_001370.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.797
• Publications: 0 publications found

Genes affected

DNAH6 (HGNC:2951): (dynein axonemal heavy chain 6) This gene belongs to the dynein family, whose members encode large proteins that are constituents of the microtubule-associated motor protein complex. This complex is composed of dynein heavy, intermediate and light chains, which can be axonemal or cytoplasmic. This protein is an axonemal dynein heavy chain. It is involved in producing force for ciliary beating by using energy from ATP hydrolysis. Mutations in this gene may cause primary ciliary dyskinesia (PCD) as well as heterotaxy. [provided by RefSeq, Jun 2016]

DNAH6 Gene-Disease associations (from GenCC):

• male infertility with azoospermia or oligozoospermia due to single gene mutation

  Inheritance: AR Classification: MODERATE Submitted by: King Faisal Specialist Hospital and Research Center

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH6	NM_001370.2	c.400-24_400-21dupTTTT		intron_variant	Intron 3 of 76	ENST00000389394.8	NP_001361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH6	ENST00000389394.8	c.400-32_400-31insTTTT		intron_variant	Intron 3 of 76	5	NM_001370.2	ENSP00000374045.3
DNAH6	ENST00000494025.1	n.229+10821_229+10822insTTTT		intron_variant	Intron 1 of 8	1
DNAH6	ENST00000468661.1	n.454+3134_454+3135insTTTT		intron_variant	Intron 3 of 3	4
DNAH6	ENST00000476689.5	n.536+3134_536+3135insTTTT		intron_variant	Intron 3 of 10	2

Frequencies

GnomAD3 genomes AF: 0.000101 AC: 15 AN: 148526 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00203

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00321

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00110 AC: 100 AN: 91098 AF XY: 0.00126

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000685

Gnomad ASJ exome AF: 0.00356

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000988

Gnomad NFE exome AF: 0.000880

Gnomad OTH exome AF: 0.00164

GnomAD4 exome AF: 0.000649 AC: 765 AN: 1179554 Hom.: 0 Cov.: 33 AF XY: 0.000665 AC XY: 385 AN XY: 579272

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 24202

American (AMR) AF: 0.000596 AC: 13 AN: 21810

Ashkenazi Jewish (ASJ) AF: 0.00201 AC: 40 AN: 19870

East Asian (EAS) AF: 0.00 AC: 0 AN: 27976

South Asian (SAS) AF: 0.00198 AC: 122 AN: 61624

European-Finnish (FIN) AF: 0.000517 AC: 21 AN: 40648

Middle Eastern (MID) AF: 0.00125 AC: 6 AN: 4792

European-Non Finnish (NFE) AF: 0.000565 AC: 526 AN: 930314

Other (OTH) AF: 0.000766 AC: 37 AN: 48318

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000101 AC: 15 AN: 148612 Hom.: 0 Cov.: 0 AF XY: 0.0000277 AC XY: 2 AN XY: 72126

African (AFR) AF: 0.00 AC: 0 AN: 40404

American (AMR) AF: 0.00 AC: 0 AN: 14940

Ashkenazi Jewish (ASJ) AF: 0.00203 AC: 7 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5030

South Asian (SAS) AF: 0.00 AC: 0 AN: 4636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9498

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67378

Other (OTH) AF: 0.00 AC: 0 AN: 2072

Alfa AF: 0.000328 Hom.: 396

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.80
La Branchor		0.96
BranchPoint Hunter		6.0
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs67469465; hg19: chr2-84755996;