chr7-21588619-C-T

Variant names:

• chr7-21588619-C-T
• rs6963535
• NM_001277115.2:c.1956C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001277115.2(DNAH11):​c.1956C>T​(p.Phe652Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,613,386 control chromosomes in the GnomAD database, including 788,992 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.99 (74936 hom., cov: 32)
  • Exomes 𝑓: 0.99 (714056 hom.)
• Consequence: DNAH11 NM_001277115.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.238
• Publications: 16 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 7-21588619-C-T is Benign according to our data. Variant chr7-21588619-C-T is described in ClinVar as Benign. ClinVar VariationId is 163097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.238 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.989 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.1956C>T	p.Phe652Phe	synonymous	Exon 11 of 82	NP_001264044.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAH11	ENST00000409508.8	TSL:5 MANE Select	c.1956C>T	p.Phe652Phe	synonymous	Exon 11 of 82	ENSP00000475939.1

Frequencies

GnomAD3 genomes AF: 0.992 AC: 150956 AN: 152188 Hom.: 74876 Cov.: 32

Gnomad AFR AF: 0.997

Gnomad AMI AF: 0.996

Gnomad AMR AF: 0.991

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.999

Gnomad MID AF: 0.984

Gnomad NFE AF: 0.989

Gnomad OTH AF: 0.986

GnomAD2 exomes AF: 0.991 AC: 246596 AN: 248948 AF XY: 0.990

Gnomad AFR exome AF: 0.997

Gnomad AMR exome AF: 0.993

Gnomad ASJ exome AF: 0.986

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.997

Gnomad NFE exome AF: 0.989

Gnomad OTH exome AF: 0.988

GnomAD4 exome AF: 0.989 AC: 1444439 AN: 1461080 Hom.: 714056 Cov.: 48 AF XY: 0.988 AC XY: 718304 AN XY: 726862

African (AFR) AF: 0.997 AC: 33374 AN: 33462

American (AMR) AF: 0.993 AC: 44412 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.987 AC: 25790 AN: 26128

East Asian (EAS) AF: 1.00 AC: 39669 AN: 39672

South Asian (SAS) AF: 0.983 AC: 84787 AN: 86240

European-Finnish (FIN) AF: 0.997 AC: 53206 AN: 53374

Middle Eastern (MID) AF: 0.976 AC: 5630 AN: 5766

European-Non Finnish (NFE) AF: 0.988 AC: 1097911 AN: 1111366

Other (OTH) AF: 0.989 AC: 59660 AN: 60354

GnomAD4 genome AF: 0.992 AC: 151076 AN: 152306 Hom.: 74936 Cov.: 32 AF XY: 0.992 AC XY: 73899 AN XY: 74472

African (AFR) AF: 0.997 AC: 41446 AN: 41570

American (AMR) AF: 0.991 AC: 15152 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3429 AN: 3472

East Asian (EAS) AF: 1.00 AC: 5178 AN: 5178

South Asian (SAS) AF: 0.982 AC: 4733 AN: 4822

European-Finnish (FIN) AF: 0.999 AC: 10605 AN: 10618

Middle Eastern (MID) AF: 0.980 AC: 288 AN: 294

European-Non Finnish (NFE) AF: 0.989 AC: 67253 AN: 68034

Other (OTH) AF: 0.986 AC: 2084 AN: 2114

Alfa AF: 0.989 Hom.: 159515

Bravo AF: 0.992

Asia WGS AF: 0.992 AC: 3449 AN: 3478

EpiCase AF: 0.986

EpiControl AF: 0.985

ClinVar

ClinVar submissions as Germline

Significance: 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)
-	-	1	Primary ciliary dyskinesia 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	2.8
DANN	Benign	0.46
PhyloP100		-0.24
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs6963535; hg19: chr7-21628237; COSMIC: COSV108124251;