rs57208694

Variant names:

• chr7-21619237-A-G
• rs57208694
• NM_001277115.2:c.4377+15A>G

Your query was ambiguous. Multiple possible variants found:

• chr7-21619237-A-G
• chr7-21619237-A-T

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.4377+15A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.477 in 1,607,068 control chromosomes in the GnomAD database, including 186,208 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19942 hom., cov: 31)
  • Exomes 𝑓: 0.47 (166266 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -1.43
• Publications: 6 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: Labcorp Genetics (formerly Invitae), ClinGen, Laboratory for Molecular Medicine
• 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=-0.89).
• BP6: Variant 7-21619237-A-G is Benign according to our data. Variant chr7-21619237-A-G is described in ClinVar as Benign. ClinVar VariationId is 93687.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.778 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.4377+15A>G		intron	N/A	NP_001264044.1	Q96DT5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.4377+15A>G		intron	N/A	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000465593.1	TSL:2	n.403+15A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.503 AC: 76339 AN: 151830 Hom.: 19917 Cov.: 31

Gnomad AFR AF: 0.595

Gnomad AMI AF: 0.447

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.382

Gnomad EAS AF: 0.799

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.331

Gnomad NFE AF: 0.463

Gnomad OTH AF: 0.475

GnomAD2 exomes AF: 0.473 AC: 114285 AN: 241688 AF XY: 0.473

Gnomad AFR exome AF: 0.591

Gnomad AMR exome AF: 0.364

Gnomad ASJ exome AF: 0.396

Gnomad EAS exome AF: 0.801

Gnomad FIN exome AF: 0.424

Gnomad NFE exome AF: 0.460

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.474 AC: 690272 AN: 1455120 Hom.: 166266 Cov.: 39 AF XY: 0.473 AC XY: 341937 AN XY: 723220

African (AFR) AF: 0.589 AC: 19627 AN: 33328

American (AMR) AF: 0.375 AC: 16277 AN: 43458

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10153 AN: 25970

East Asian (EAS) AF: 0.763 AC: 30184 AN: 39542

South Asian (SAS) AF: 0.455 AC: 38828 AN: 85260

European-Finnish (FIN) AF: 0.428 AC: 22732 AN: 53134

Middle Eastern (MID) AF: 0.411 AC: 2365 AN: 5756

European-Non Finnish (NFE) AF: 0.470 AC: 521047 AN: 1108526

Other (OTH) AF: 0.483 AC: 29059 AN: 60146

GnomAD4 genome AF: 0.503 AC: 76412 AN: 151948 Hom.: 19942 Cov.: 31 AF XY: 0.500 AC XY: 37151 AN XY: 74268

African (AFR) AF: 0.595 AC: 24657 AN: 41418

American (AMR) AF: 0.438 AC: 6682 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.382 AC: 1323 AN: 3466

East Asian (EAS) AF: 0.798 AC: 4110 AN: 5148

South Asian (SAS) AF: 0.475 AC: 2286 AN: 4810

European-Finnish (FIN) AF: 0.417 AC: 4408 AN: 10576

Middle Eastern (MID) AF: 0.332 AC: 97 AN: 292

European-Non Finnish (NFE) AF: 0.463 AC: 31438 AN: 67956

Other (OTH) AF: 0.475 AC: 1004 AN: 2114

Alfa AF: 0.469 Hom.: 3182

Bravo AF: 0.509

Asia WGS AF: 0.618 AC: 2152 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not specified (3)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.5
DANN	Benign	0.33
PhyloP100		-1.4
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: rs57208694; hg19: chr7-21658855; COSMIC: COSV60937581;