chr7-21606637-C-T

Variant names:

• chr7-21606637-C-T
• rs886038464
• NM_001277115.2:c.3766-10C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001277115.2(DNAH11):​c.3766-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 16)
  • Exomes 𝑓: 0.000029 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DNAH11 NM_001277115.2 intron
• Scores: Splicing: ADA: 0.00003773
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.752
• Publications: 0 publications found

Genes affected

DNAH11 (HGNC:2942): (dynein axonemal heavy chain 11) This gene encodes a ciliary outer dynein arm protein and is a member of the dynein heavy chain family. It is a microtubule-dependent motor ATPase and has been reported to be involved in the movement of respiratory cilia. Mutations in this gene have been implicated in causing Kartagener Syndrome (a combination of situs inversus totalis and Primary Ciliary Dyskinesia (PCD), also called Immotile Cilia Syndrome 1 (ICS1)) and male sterility. [provided by RefSeq, Mar 2013]

DNAH11 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 7

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.3766-10C>T		intron_variant	Intron 19 of 81	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.3766-10C>T		intron_variant	Intron 19 of 81	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.00129 AC: 88 AN: 67958 Hom.: 0 Cov.: 16

Gnomad AFR AF: 0.000850

Gnomad AMI AF: 0.00214

Gnomad AMR AF: 0.00168

Gnomad ASJ AF: 0.000992

Gnomad EAS AF: 0.00103

Gnomad SAS AF: 0.000421

Gnomad FIN AF: 0.00410

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00129

Gnomad OTH AF: 0.00119

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000293 AC: 22 AN: 749636 Hom.: 0 Cov.: 24 AF XY: 0.0000371 AC XY: 14 AN XY: 377630

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

African (AFR) AF: 0.0000561 AC: 1 AN: 17810

American (AMR) AF: 0.000270 AC: 5 AN: 18518

Ashkenazi Jewish (ASJ) AF: 0.000134 AC: 2 AN: 14980

East Asian (EAS) AF: 0.0000756 AC: 2 AN: 26470

South Asian (SAS) AF: 0.00 AC: 0 AN: 47998

European-Finnish (FIN) AF: 0.0000308 AC: 1 AN: 32520

Middle Eastern (MID) AF: 0.000386 AC: 1 AN: 2594

European-Non Finnish (NFE) AF: 0.0000162 AC: 9 AN: 554298

Other (OTH) AF: 0.0000290 AC: 1 AN: 34448

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.00129 AC: 88 AN: 68000 Hom.: 0 Cov.: 16 AF XY: 0.00135 AC XY: 43 AN XY: 31768

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

African (AFR) AF: 0.000847 AC: 14 AN: 16524

American (AMR) AF: 0.00167 AC: 10 AN: 5972

Ashkenazi Jewish (ASJ) AF: 0.000992 AC: 2 AN: 2016

East Asian (EAS) AF: 0.00103 AC: 2 AN: 1934

South Asian (SAS) AF: 0.000423 AC: 1 AN: 2364

European-Finnish (FIN) AF: 0.00410 AC: 12 AN: 2924

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 84

European-Non Finnish (NFE) AF: 0.00129 AC: 45 AN: 34866

Other (OTH) AF: 0.00118 AC: 1 AN: 848

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.24
DANN	Benign	0.13
PhyloP100		-0.75

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000038
dbscSNV1_RF	Benign	0.0060
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: rs886038464; hg19: chr7-21646255;