rs10950854

Variant names:

• chr7-21559615-C-T
• rs10950854
• NM_001277115.2:c.705C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-21559615-C-T
• chr7-21559615-C-G

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.705C>T​(p.Asn235Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,593,732 control chromosomes in the GnomAD database, including 158,726 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16846 hom., cov: 32)
  • Exomes 𝑓: 0.44 (141880 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.401
• Publications: 18 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.38).
• BP6: Variant 7-21559615-C-T is Benign according to our data. Variant chr7-21559615-C-T is described in ClinVar as Benign. ClinVar VariationId is 93693.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.401 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.729 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.705C>T	p.Asn235Asn	synonymous	Exon 4 of 82	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.705C>T	p.Asn235Asn	synonymous	Exon 4 of 82	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000483691.1	TSL:3	n.-100C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70261 AN: 151730 Hom.: 16817 Cov.: 32

Gnomad AFR AF: 0.541

Gnomad AMI AF: 0.210

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.749

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.386

Gnomad MID AF: 0.417

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.456

GnomAD2 exomes AF: 0.447 AC: 105203 AN: 235568 AF XY: 0.450

Gnomad AFR exome AF: 0.533

Gnomad AMR exome AF: 0.321

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.746

Gnomad FIN exome AF: 0.386

Gnomad NFE exome AF: 0.422

Gnomad OTH exome AF: 0.414

GnomAD4 exome AF: 0.438 AC: 631657 AN: 1441884 Hom.: 141880 Cov.: 32 AF XY: 0.440 AC XY: 314957 AN XY: 716552

African (AFR) AF: 0.537 AC: 17634 AN: 32846

American (AMR) AF: 0.335 AC: 14229 AN: 42426

Ashkenazi Jewish (ASJ) AF: 0.407 AC: 10540 AN: 25872

East Asian (EAS) AF: 0.699 AC: 27459 AN: 39260

South Asian (SAS) AF: 0.530 AC: 43502 AN: 82006

European-Finnish (FIN) AF: 0.393 AC: 20872 AN: 53106

Middle Eastern (MID) AF: 0.452 AC: 2589 AN: 5732

European-Non Finnish (NFE) AF: 0.425 AC: 467775 AN: 1100982

Other (OTH) AF: 0.454 AC: 27057 AN: 59654

GnomAD4 genome AF: 0.463 AC: 70339 AN: 151848 Hom.: 16846 Cov.: 32 AF XY: 0.464 AC XY: 34432 AN XY: 74204

African (AFR) AF: 0.542 AC: 22424 AN: 41366

American (AMR) AF: 0.384 AC: 5863 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3466

East Asian (EAS) AF: 0.749 AC: 3874 AN: 5172

South Asian (SAS) AF: 0.542 AC: 2607 AN: 4814

European-Finnish (FIN) AF: 0.386 AC: 4067 AN: 10528

Middle Eastern (MID) AF: 0.424 AC: 123 AN: 290

European-Non Finnish (NFE) AF: 0.425 AC: 28869 AN: 67936

Other (OTH) AF: 0.457 AC: 961 AN: 2104

Alfa AF: 0.425 Hom.: 27479

Bravo AF: 0.463

Asia WGS AF: 0.628 AC: 2185 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	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	-0.38
CADD	Benign	3.8
DANN	Benign	0.65
PhyloP100		0.40
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: rs10950854; hg19: chr7-21599233; COSMIC: COSV60940505; COSMIC: COSV60940505;