Genetic Variant DYNC1I1:c.224-141_224-140delTT (chr7-95813093-CTT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001135556.2(DYNC1I1):c.224-141_224-140delTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,105,664 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000028 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0034 ( 0 hom. )

Consequence

DYNC1I1
NM_001135556.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.361

Publications

0 publications found

Variant links:

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

DYNC1I1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Variant has high frequency in the SAS (0.00527) population. However there is too low homozygotes in high coverage region: (expected more than 2, got 0).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYNC1I1	NM_001135556.2	MANE Select	c.224-141_224-140delTT	intron	N/A	NP_001129028.1	O14576-2
DYNC1I1	NM_004411.5		c.224-90_224-89delTT	intron	N/A	NP_004402.1	O14576-1
DYNC1I1	NM_001278421.2		c.224-90_224-89delTT	intron	N/A	NP_001265350.1	O14576-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.224-153_224-152delTT	intron	N/A	ENSP00000392337.2	O14576-2
DYNC1I1	ENST00000324972.10	TSL:1	c.224-102_224-101delTT	intron	N/A	ENSP00000320130.6	O14576-1
DYNC1I1	ENST00000457059.2	TSL:1	c.224-153_224-152delTT	intron	N/A	ENSP00000412444.1	O14576-2

Frequencies

GnomAD3 genomes

AF:

0.0000285

AC:

AN:

140372

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000525

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000206

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00343

AC:

3315

AN:

965280

Hom.:

AF XY:

0.00350

AC XY:

1682

AN XY:

480106

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00289

AC:

AN:

18684

American (AMR)

AF:

0.00422

AC:

AN:

17290

Ashkenazi Jewish (ASJ)

AF:

0.00546

AC:

AN:

16670

East Asian (EAS)

AF:

0.00434

AC:

114

AN:

26296

South Asian (SAS)

AF:

0.00582

AC:

284

AN:

48776

European-Finnish (FIN)

AF:

0.00558

AC:

168

AN:

30120

Middle Eastern (MID)

AF:

0.00206

AC:

AN:

2914

European-Non Finnish (NFE)

AF:

0.00311

AC:

2374

AN:

764500

Other (OTH)

AF:

0.00377

AC:

151

AN:

40030

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.264

Heterozygous variant carriers

359

718

1076

1435

1794

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.0000285

AC:

AN:

140384

Hom.:

Cov.:

AF XY:

0.0000444

AC XY:

AN XY:

67578

show subpopulations

African (AFR)

AF:

0.0000524

AC:

AN:

38172

American (AMR)

AF:

0.00

AC:

AN:

13892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3382

East Asian (EAS)

AF:

0.000207

AC:

AN:

4832

South Asian (SAS)

AF:

0.00

AC:

AN:

4496

European-Finnish (FIN)

AF:

0.00

AC:

AN:

7086

Middle Eastern (MID)

AF:

0.00

AC:

AN:

270

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

65424

Other (OTH)

AF:

0.00

AC:

AN:

1938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.00

Hom.:

272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.36

Mutation Taster

=99/1

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

7-95813093-CTTTTT-CTTT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over