rs191073674

Variant names:

• chr7-21867849-T-A
• rs191073674
• NM_001277115.2:c.11691-10T>A

Your query was ambiguous. Multiple possible variants found:

• chr7-21867849-T-A
• chr7-21867849-T-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_001277115.2(DNAH11):​c.11691-10T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000153 in 1,559,392 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00076 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000087 (1 hom.)
• Consequence: DNAH11 NM_001277115.2 intron
• Scores: Splicing: ADA: 0.0002885
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.450
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 7-21867849-T-A is Benign according to our data. Variant chr7-21867849-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 454641.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH11	NM_001277115.2	c.11691-10T>A		intron_variant	Intron 71 of 81	ENST00000409508.8	NP_001264044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH11	ENST00000409508.8	c.11691-10T>A		intron_variant	Intron 71 of 81	5	NM_001277115.2	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.000757 AC: 115 AN: 152014 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00271

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000159 AC: 27 AN: 170274 AF XY: 0.000144

Gnomad AFR exome AF: 0.00230

Gnomad AMR exome AF: 0.0000776

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000437

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000874 AC: 123 AN: 1407260 Hom.: 1 Cov.: 35 AF XY: 0.0000734 AC XY: 51 AN XY: 694896

African (AFR) AF: 0.00303 AC: 97 AN: 32026

American (AMR) AF: 0.0000544 AC: 2 AN: 36736

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25278

East Asian (EAS) AF: 0.00 AC: 0 AN: 36818

South Asian (SAS) AF: 0.0000125 AC: 1 AN: 79682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49960

Middle Eastern (MID) AF: 0.000351 AC: 2 AN: 5700

European-Non Finnish (NFE) AF: 0.00000739 AC: 8 AN: 1082694

Other (OTH) AF: 0.000223 AC: 13 AN: 58366

GnomAD4 genome AF: 0.000756 AC: 115 AN: 152132 Hom.: 0 Cov.: 30 AF XY: 0.000672 AC XY: 50 AN XY: 74356

African (AFR) AF: 0.00270 AC: 112 AN: 41522

American (AMR) AF: 0.000131 AC: 2 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67986

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000884

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia Benign:1

Nov 27, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		0.45
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00029
dbscSNV1_RF	Benign	0.15
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: rs191073674; hg19: chr7-21907467;