7-21704421-T-G

Variant names:

• chr7-21704421-T-G
• rs2965401
• NM_001277115.2:c.6274-13T>G

Variant summary

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

The NM_001277115.2(DNAH11):​c.6274-13T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.273 in 1,594,826 control chromosomes in the GnomAD database, including 83,296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (19302 hom., cov: 32)
  • Exomes 𝑓: 0.26 (63994 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.03
• Publications: 7 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-21704421-T-G is Benign according to our data. Variant chr7-21704421-T-G is described in ClinVar as Benign. ClinVar VariationId is 163107.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.806 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001277115.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	NM_001277115.2	MANE Select	c.6274-13T>G		intron	N/A	NP_001264044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.6274-13T>G		intron	N/A	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64308 AN: 151594 Hom.: 19247 Cov.: 32

Gnomad AFR AF: 0.813

Gnomad AMI AF: 0.150

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.175

Gnomad EAS AF: 0.739

Gnomad SAS AF: 0.450

Gnomad FIN AF: 0.275

Gnomad MID AF: 0.288

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.359

GnomAD2 exomes AF: 0.390 AC: 82505 AN: 211530 AF XY: 0.373

Gnomad AFR exome AF: 0.835

Gnomad AMR exome AF: 0.564

Gnomad ASJ exome AF: 0.193

Gnomad EAS exome AF: 0.758

Gnomad FIN exome AF: 0.296

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.317

GnomAD4 exome AF: 0.257 AC: 370622 AN: 1443116 Hom.: 63994 Cov.: 31 AF XY: 0.258 AC XY: 185001 AN XY: 716308

African (AFR) AF: 0.839 AC: 27560 AN: 32852

American (AMR) AF: 0.524 AC: 21742 AN: 41474

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 4484 AN: 25740

East Asian (EAS) AF: 0.767 AC: 30158 AN: 39320

South Asian (SAS) AF: 0.428 AC: 35350 AN: 82634

European-Finnish (FIN) AF: 0.274 AC: 14471 AN: 52788

Middle Eastern (MID) AF: 0.293 AC: 1680 AN: 5736

European-Non Finnish (NFE) AF: 0.197 AC: 217347 AN: 1102850

Other (OTH) AF: 0.299 AC: 17830 AN: 59722

GnomAD4 genome AF: 0.425 AC: 64433 AN: 151710 Hom.: 19302 Cov.: 32 AF XY: 0.431 AC XY: 31990 AN XY: 74144

African (AFR) AF: 0.813 AC: 33691 AN: 41428

American (AMR) AF: 0.442 AC: 6727 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.175 AC: 607 AN: 3466

East Asian (EAS) AF: 0.738 AC: 3806 AN: 5156

South Asian (SAS) AF: 0.451 AC: 2159 AN: 4784

European-Finnish (FIN) AF: 0.275 AC: 2897 AN: 10524

Middle Eastern (MID) AF: 0.293 AC: 86 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13563 AN: 67824

Other (OTH) AF: 0.362 AC: 761 AN: 2100

Alfa AF: 0.290 Hom.: 1788

Bravo AF: 0.453

Asia WGS AF: 0.601 AC: 2088 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not provided (1)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.3
DANN	Benign	0.58
PhyloP100		1.0
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: rs2965401; hg19: chr7-21744039;