Variant 11-72838859-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_014824.3(FCHSD2):c.2155C>G(p.Pro719Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000236 in 1,607,414 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

FCHSD2
NM_014824.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

Variant links:

Genes affected

FCHSD2 (HGNC:29114): (FCH and double SH3 domains 2) Enables phosphatidylinositol-3,4,5-trisphosphate binding activity and phosphatidylinositol-3,4-bisphosphate binding activity. Involved in clathrin-dependent endocytosis and positive regulation of Arp2/3 complex-mediated actin nucleation. Located in plasma membrane. Colocalizes with clathrin-coated pit. [provided by Alliance of Genome Resources, Apr 2022]

FCHSD2 links:

ATG16L2 (HGNC:25464): (autophagy related 16 like 2) Predicted to be involved in autophagosome assembly and negative stranded viral RNA replication. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ATG16L2 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.34234282).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCHSD2	NM_014824.3 linkuse as main transcript	c.2155C>G	p.Pro719Ala	missense_variant	20/20	ENST00000409418.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCHSD2	ENST00000409418.9 linkuse as main transcript	c.2155C>G	p.Pro719Ala	missense_variant	20/20	2	NM_014824.3	P1	O94868-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000126

AC:

AN:

238004

Hom.:

AF XY:

0.00000778

AC XY:

AN XY:

128490

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000299

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000186

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000247

AC:

AN:

1455648

Hom.:

Cov.:

AF XY:

0.0000290

AC XY:

AN XY:

723126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000228

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000306

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151766

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74146

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000295

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Feb 06, 2023

The c.2155C>G (p.P719A) alteration is located in exon 20 (coding exon 20) of the FCHSD2 gene. This alteration results from a C to G substitution at nucleotide position 2155, causing the proline (P) at amino acid position 719 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.071

BayesDel_noAF

Benign

-0.25

Cadd

Pathogenic

Dann

Uncertain

1.0

Eigen

Pathogenic

0.74

Eigen_PC

Pathogenic

0.81

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.95

D;D;D;D;D

M_CAP

Benign

0.0071

MetaRNN

Benign

0.34

T;T;T;T;T

MetaSVM

Benign

-1.2

MutationTaster

Benign

1.0

D;D;D;D;D;D

PrimateAI

Uncertain

0.59

PROVEAN

Uncertain

-4.2

D;D;D;D;D

REVEL

Benign

0.24

Sift

Pathogenic

0.0

D;D;D;D;D

Sift4G

Pathogenic

0.0

D;D;D;D;D

Polyphen

1.0, 1.0

.;.;D;.;D

Vest4

0.45

MVP

0.56

MPC

0.35

ClinPred

0.65

GERP RS

6.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.31

gMVP

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over