5-55220462-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001190787.3(MCIDAS):c.1062C>T(p.Ser354Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00211 in 1,536,076 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 21 hom. )

Consequence

MCIDAS
NM_001190787.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0820

Publications

0 publications found

Variant links:

Genes affected

MCIDAS (HGNC:40050): (multiciliate differentiation and DNA synthesis associated cell cycle protein) This gene encodes a member of the geminin family of proteins. The encoded nuclear protein is required for the generation of multiciliated cells in respiratory epithelium. Mutations in this gene cause a rare mucociliary clearance disorder associated with recurring respiratory infections in human patients, known as reduced generation of multiple motile cilia (RGMC). [provided by RefSeq, Sep 2016]

MCIDAS Gene-Disease associations (from GenCC):

ciliary dyskinesia, primary, 42
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen, PanelApp Australia
primary ciliary dyskinesia
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MCIDAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.45).

BP6

Variant 5-55220462-G-A is Benign according to our data. Variant chr5-55220462-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 238617.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.082 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00141 (215/152296) while in subpopulation SAS AF = 0.00994 (48/4828). AF 95% confidence interval is 0.0077. There are 1 homozygotes in GnomAd4. There are 116 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 21 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MCIDAS	NM_001190787.3 link	c.1062C>T	p.Ser354Ser	synonymous_variant	Exon 7 of 7	ENST00000513312.3	NP_001177716.1	D6RGH6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MCIDAS	ENST00000513312.3 link	c.1062C>T	p.Ser354Ser	synonymous_variant	Exon 7 of 7	1	NM_001190787.3	ENSP00000426359.1	D6RGH6
MCIDAS	ENST00000513468.5 link	n.*526C>T		non_coding_transcript_exon_variant	Exon 7 of 7	5		ENSP00000422165.1	I6L8E2
MCIDAS	ENST00000513468.5 link	n.*526C>T		3_prime_UTR_variant	Exon 7 of 7	5		ENSP00000422165.1	I6L8E2

Frequencies

GnomAD3 genomes

AF:

0.00141

AC:

215

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.00993

Gnomad FIN

AF:

0.00104

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00165

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.00296

AC:

399

AN:

134914

AF XY:

0.00353

show subpopulations

Gnomad AFR exome

AF:

0.000459

Gnomad AMR exome

AF:

0.00102

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000951

Gnomad FIN exome

AF:

0.000557

Gnomad NFE exome

AF:

0.00158

Gnomad OTH exome

AF:

0.00192

GnomAD4 exome

AF:

0.00218

AC:

3021

AN:

1383780

Hom.:

Cov.:

AF XY:

0.00255

AC XY:

1739

AN XY:

682828

show subpopulations

African (AFR)

AF:

0.000253

AC:

AN:

31594

American (AMR)

AF:

0.000896

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.00

AC:

AN:

35734

South Asian (SAS)

AF:

0.0123

AC:

975

AN:

79234

European-Finnish (FIN)

AF:

0.000354

AC:

AN:

33916

Middle Eastern (MID)

AF:

0.00514

AC:

AN:

5640

European-Non Finnish (NFE)

AF:

0.00172

AC:

1851

AN:

1078882

Other (OTH)

AF:

0.00197

AC:

114

AN:

57898

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

206

412

619

825

1031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

160

240

320

400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00141

AC:

215

AN:

152296

Hom.:

Cov.:

AF XY:

0.00156

AC XY:

116

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000313

AC:

AN:

41562

American (AMR)

AF:

0.00183

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.000387

AC:

AN:

5166

South Asian (SAS)

AF:

0.00994

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00104

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00165

AC:

112

AN:

68022

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.000990

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Primary ciliary dyskinesia

Benign:1

Jan 27, 2025

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

-0.45

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

0.082

Mutation Taster

=100/0

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over