chr17-19336119-C-T

Variant names:

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014964.5(EPN2):c.*1865C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 152,198 control chromosomes in the GnomAD database, including 30,697 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.56 ( 30683 hom., cov: 32)

Exomes 𝑓: 0.66 ( 14 hom. )

Consequence

EPN2
NM_014964.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.821

Publications

17 publications found

Variant links:

Genes affected

EPN2 (HGNC:18639): (epsin 2) This gene encodes a protein which interacts with clathrin and adaptor-related protein complex 2, alpha 1 subunit. The protein is found in a brain-derived clathrin-coated vesicle fraction and localizes to the peri-Golgi region and the cell periphery. The protein is thought to be involved in clathrin-mediated endocytosis. Alternate splicing of this gene results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

EPN2 links:

B9D1 (HGNC:24123): (B9 domain containing 1) This gene encodes a B9 domain-containing protein, one of several that are involved in ciliogenesis. Alterations in expression of this gene have been found in a family with Meckel syndrome. Meckel syndrome has been associated with at least six different genes. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Mar 2016]

B9D1 Gene-Disease associations (from GenCC):

ciliopathy
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, PanelApp Australia
Joubert syndrome 27
Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
Meckel syndrome, type 9
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, G2P
Joubert syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Meckel syndrome
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

B9D1 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_014964.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.803 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014964.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPN2	NM_014964.5	MANE Select	c.*1865C>T	3_prime_UTR	Exon 11 of 11	NP_055779.2	O95208-1
EPN2	NM_148921.4		c.*1865C>T	3_prime_UTR	Exon 10 of 10	NP_683723.2	O95208-2
EPN2	NM_001102664.2		c.*1865C>T	3_prime_UTR	Exon 8 of 8	NP_001096134.1	O95208-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
EPN2	ENST00000314728.10	TSL:1 MANE Select	c.*1865C>T	3_prime_UTR	Exon 11 of 11	ENSP00000320543.5	O95208-1
EPN2	ENST00000898662.1		c.*1865C>T	3_prime_UTR	Exon 11 of 11	ENSP00000568721.1
EPN2	ENST00000347697.6	TSL:5	c.*1865C>T	3_prime_UTR	Exon 10 of 10	ENSP00000261495.3	O95208-2

Frequencies

GnomAD3 genomes

AF:

0.556

AC:

84594

AN:

152022

Hom.:

30689

Cov.:

show subpopulations

Gnomad AFR

AF:

0.151

Gnomad AMI

AF:

0.940

Gnomad AMR

AF:

0.537

Gnomad ASJ

AF:

0.843

Gnomad EAS

AF:

0.00597

Gnomad SAS

AF:

0.341

Gnomad FIN

AF:

0.778

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.808

Gnomad OTH

AF:

0.617

GnomAD4 exome

AF:

0.655

AC:

AN:

Hom.:

Cov.:

AF XY:

0.720

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.783

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.555

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.556

AC:

84577

AN:

152140

Hom.:

30683

Cov.:

AF XY:

0.545

AC XY:

40541

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.150

AC:

6238

AN:

41500

American (AMR)

AF:

0.536

AC:

8194

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.843

AC:

2920

AN:

3464

East Asian (EAS)

AF:

0.00598

AC:

AN:

5184

South Asian (SAS)

AF:

0.343

AC:

1653

AN:

4816

European-Finnish (FIN)

AF:

0.778

AC:

8236

AN:

10590

Middle Eastern (MID)

AF:

0.660

AC:

194

AN:

294

European-Non Finnish (NFE)

AF:

0.808

AC:

54967

AN:

67994

Other (OTH)

AF:

0.609

AC:

1287

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1213

2426

3639

4852

6065

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.698

Hom.:

69674

Bravo

AF:

0.523

Asia WGS

AF:

0.168

AC:

585

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.63

(source)

DANN

Benign

0.54

PhyloP100

-0.82

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over