rs72657303

chr7-21600720-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_001277115.2(DNAH11):c.3045G>T(p.Glu1015Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00425 in 1,613,798 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0044 (21 hom.)
• Consequence: DNAH11 NM_001277115.2 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.60

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.00851959).
• BP6: Variant 7-21600720-G-T is Benign according to our data. Variant chr7-21600720-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 238905.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00297 (452/152264) while in subpopulation NFE AF= 0.00526 (358/68024). AF 95% confidence interval is 0.00481. There are 1 homozygotes in gnomad4. There are 195 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNAH11	NM_001277115.2	c.3045G>T	p.Glu1015Asp	missense_variant	16/82	ENST00000409508.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNAH11	ENST00000409508.8	c.3045G>T	p.Glu1015Asp	missense_variant	16/82	5	NM_001277115.2	P1

Frequencies

GnomAD3 genomes AF: 0.00297 AC: 452 AN: 152146 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00144

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00339

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00526

Gnomad OTH AF: 0.000958

GnomAD3 exomes AF: 0.00300 AC: 745 AN: 248626 Hom.: 3 AF XY: 0.00277 AC XY: 374 AN XY: 134846

Gnomad AFR exome AF: 0.000969

Gnomad AMR exome AF: 0.000522

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00302

Gnomad NFE exome AF: 0.00560

Gnomad OTH exome AF: 0.00282

GnomAD4 exome AF: 0.00438 AC: 6405 AN: 1461534 Hom.: 21 Cov.: 30 AF XY: 0.00418 AC XY: 3036 AN XY: 727056

Gnomad4 AFR exome AF: 0.000657

Gnomad4 AMR exome AF: 0.000537

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.00335

Gnomad4 NFE exome AF: 0.00540

Gnomad4 OTH exome AF: 0.00283

GnomAD4 genome AF: 0.00297 AC: 452 AN: 152264 Hom.: 1 Cov.: 32 AF XY: 0.00262 AC XY: 195 AN XY: 74456

Gnomad4 AFR AF: 0.000770

Gnomad4 AMR AF: 0.00144

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00339

Gnomad4 NFE AF: 0.00526

Gnomad4 OTH AF: 0.000948

Alfa AF: 0.00426 Hom.: 6

Bravo AF: 0.00286

TwinsUK AF: 0.00674 AC: 25

ALSPAC AF: 0.00467 AC: 18

ESP6500AA AF: 0.00102 AC: 4

ESP6500EA AF: 0.00540 AC: 45

ExAC AF: 0.00332 AC: 402

EpiCase AF: 0.00442

EpiControl AF: 0.00480

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Dec 01, 2023	DNAH11: BP4, BS2 -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 15, 2021	This variant is associated with the following publications: (PMID: 32859249) -

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Primary ciliary dyskinesia 7 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Apr 21, 2022

- -

Primary ciliary dyskinesia Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.55
Cadd	Benign	17
Dann	Uncertain	0.99
Eigen	Benign	0.13
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.41	T;T;T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.0085	T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	0.82	D
PrimateAI	Benign	0.32	T
Polyphen		0.92	.;.;P
Vest4		0.36
MutPred		0.51		Gain of MoRF binding (P = 0.1357);Gain of MoRF binding (P = 0.1357);Gain of MoRF binding (P = 0.1357);
MVP		0.33
ClinPred		0.015	T
GERP RS		4.8
Varity_R		0.11
gMVP		0.41

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs72657303; hg19: chr7-21640338; COSMIC: COSV99080607;