rs57952953

Variant names:

• chr7-21619936-A-ATTAAT
• rs57952953
• NM_001277115.2:c.4378-17_4378-16insATTTA

Your query was ambiguous. Multiple possible variants found:

• chr7-21619936-A-ATTAAT
• chr7-21619936-A-ATTACT

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001277115.2(DNAH11):​c.4378-17_4378-16insATTTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.42 in 1,559,650 control chromosomes in the GnomAD database, including 142,372 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15627 hom., cov: 0)
  • Exomes 𝑓: 0.42 (126745 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: 0.774
• 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), Laboratory for Molecular Medicine, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 7-21619936-A-ATTAAT is Benign according to our data. Variant chr7-21619936-A-ATTAAT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 93688.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.74 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.4378-17_4378-16insATTTA		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.4378-20_4378-19insTTAAT		intron	N/A	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000465593.1	TSL:2	n.404-20_404-19insTTAAT		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67579 AN: 151354 Hom.: 15616 Cov.: 0

Gnomad AFR AF: 0.517

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.406

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.760

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.303

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.425

GnomAD2 exomes AF: 0.407 AC: 88438 AN: 217250 AF XY: 0.407

Gnomad AFR exome AF: 0.503

Gnomad AMR exome AF: 0.297

Gnomad ASJ exome AF: 0.331

Gnomad EAS exome AF: 0.735

Gnomad FIN exome AF: 0.379

Gnomad NFE exome AF: 0.395

Gnomad OTH exome AF: 0.382

GnomAD4 exome AF: 0.417 AC: 587654 AN: 1408178 Hom.: 126745 Cov.: 30 AF XY: 0.416 AC XY: 291293 AN XY: 700296

African (AFR) AF: 0.496 AC: 15275 AN: 30766

American (AMR) AF: 0.326 AC: 11667 AN: 35806

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8528 AN: 25126

East Asian (EAS) AF: 0.726 AC: 27623 AN: 38036

South Asian (SAS) AF: 0.389 AC: 29992 AN: 77198

European-Finnish (FIN) AF: 0.387 AC: 20554 AN: 53066

Middle Eastern (MID) AF: 0.368 AC: 2088 AN: 5668

European-Non Finnish (NFE) AF: 0.412 AC: 446850 AN: 1083968

Other (OTH) AF: 0.428 AC: 25077 AN: 58544

GnomAD4 genome AF: 0.446 AC: 67631 AN: 151472 Hom.: 15627 Cov.: 0 AF XY: 0.444 AC XY: 32884 AN XY: 73988

African (AFR) AF: 0.517 AC: 21325 AN: 41254

American (AMR) AF: 0.405 AC: 6177 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1168 AN: 3454

East Asian (EAS) AF: 0.760 AC: 3869 AN: 5094

South Asian (SAS) AF: 0.413 AC: 1988 AN: 4810

European-Finnish (FIN) AF: 0.376 AC: 3947 AN: 10500

Middle Eastern (MID) AF: 0.301 AC: 88 AN: 292

European-Non Finnish (NFE) AF: 0.410 AC: 27817 AN: 67820

Other (OTH) AF: 0.425 AC: 896 AN: 2106

Alfa AF: 0.411 Hom.: 2196

Asia WGS AF: 0.564 AC: 1962 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Primary ciliary dyskinesia (2)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs57952953;

hg19: chr7-21659554;

COSMIC: COSV104410039;