rs1043809

Variant names:

• chr17-19336119-C-T
• rs1043809
• NM_014964.5:c.*1865C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.821
• Publications: 17 publications found

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]

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 Submitted by: ClinGen
• Joubert syndrome 27

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Meckel syndrome, type 9

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: G2P, Genomics England PanelApp
• Joubert syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Meckel syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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.: 32

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: 38 AN: 58 Hom.: 14 Cov.: 0 AF XY: 0.720 AC XY: 36 AN XY: 50

African (AFR) AF: 0.00 AC: 0 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.783 AC: 36 AN: 46

Other (OTH) AF: 0.250 AC: 1 AN: 4

GnomAD4 genome AF: 0.556 AC: 84577 AN: 152140 Hom.: 30683 Cov.: 32 AF XY: 0.545 AC XY: 40541 AN XY: 74362

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: 31 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

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
DANN	Benign	0.54
PhyloP100		-0.82
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1043809; hg19: chr17-19239432;