rs72658822

Variant names:

• chr7-21892413-T-C
• rs72658822
• NM_001277115.2:c.12508-12T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-21892413-T-C
• chr7-21892413-T-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.12508-12T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0183 in 1,596,596 control chromosomes in the GnomAD database, including 457 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.031 (115 hom., cov: 32)
  • Exomes 𝑓: 0.017 (342 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Scores: Splicing: ADA: 0.0002397
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 0.300
• Publications: 4 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=-0.73).
• BP6: Variant 7-21892413-T-C is Benign according to our data. Variant chr7-21892413-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 178736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0624 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.12508-12T>C		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.12508-12T>C		intron	N/A	ENSP00000475939.1	Q96DT5
	DNAH11	ENST00000479878.1	TSL:3	n.-212T>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0308 AC: 4687 AN: 152112 Hom.: 114 Cov.: 32

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0343

Gnomad EAS AF: 0.0222

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0124

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0150

Gnomad OTH AF: 0.0310

GnomAD2 exomes AF: 0.0217 AC: 5235 AN: 241500 AF XY: 0.0219

Gnomad AFR exome AF: 0.0648

Gnomad AMR exome AF: 0.0164

Gnomad ASJ exome AF: 0.0304

Gnomad EAS exome AF: 0.0176

Gnomad FIN exome AF: 0.0118

Gnomad NFE exome AF: 0.0155

Gnomad OTH exome AF: 0.0257

GnomAD4 exome AF: 0.0170 AC: 24495 AN: 1444366 Hom.: 342 Cov.: 30 AF XY: 0.0176 AC XY: 12625 AN XY: 715580

African (AFR) AF: 0.0656 AC: 2162 AN: 32964

American (AMR) AF: 0.0165 AC: 712 AN: 43262

Ashkenazi Jewish (ASJ) AF: 0.0295 AC: 748 AN: 25396

East Asian (EAS) AF: 0.0151 AC: 592 AN: 39334

South Asian (SAS) AF: 0.0340 AC: 2890 AN: 84884

European-Finnish (FIN) AF: 0.0115 AC: 607 AN: 52984

Middle Eastern (MID) AF: 0.0321 AC: 182 AN: 5670

European-Non Finnish (NFE) AF: 0.0139 AC: 15260 AN: 1100358

Other (OTH) AF: 0.0225 AC: 1342 AN: 59514

GnomAD4 genome AF: 0.0309 AC: 4697 AN: 152230 Hom.: 115 Cov.: 32 AF XY: 0.0310 AC XY: 2310 AN XY: 74420

African (AFR) AF: 0.0645 AC: 2677 AN: 41530

American (AMR) AF: 0.0268 AC: 409 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 119 AN: 3472

East Asian (EAS) AF: 0.0218 AC: 113 AN: 5174

South Asian (SAS) AF: 0.0290 AC: 140 AN: 4822

European-Finnish (FIN) AF: 0.0124 AC: 132 AN: 10614

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0150 AC: 1020 AN: 68012

Other (OTH) AF: 0.0321 AC: 68 AN: 2116

Alfa AF: 0.0190 Hom.: 44

Bravo AF: 0.0333

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00024
dbscSNV1_RF	Benign	0.062
SpliceAI score (max)		0.11		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: rs72658822; hg19: chr7-21932031;