Variant 16-2899070-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138439.3(FLYWCH2):c.344G>A(p.Ser115Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000452 in 1,613,788 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000027 ( 1 hom. )

Consequence

FLYWCH2
NM_138439.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.152

Variant links:

Genes affected

FLYWCH2 (HGNC:25178): (FLYWCH family member 2) Enables RNA binding activity. [provided by Alliance of Genome Resources, Apr 2022]

FLYWCH2 links:

FLYWCH2 (HGNC:):

FLYWCH2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.009660631).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FLYWCH2	NM_138439.3 linkuse as main transcript	c.344G>A	p.Ser115Asn	missense_variant	4/4	ENST00000396958.8	NP_612448.1	Q96CP2
FLYWCH2	NM_001142499.1 linkuse as main transcript	c.344G>A	p.Ser115Asn	missense_variant	4/4		NP_001135971.1	Q96CP2
FLYWCH2	NM_001142500.1 linkuse as main transcript	c.344G>A	p.Ser115Asn	missense_variant	4/4		NP_001135972.1	Q96CP2
FLYWCH2	XM_005255078.6 linkuse as main transcript	c.344G>A	p.Ser115Asn	missense_variant	3/3		XP_005255135.1	Q96CP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
FLYWCH2	ENST00000396958.8 linkuse as main transcript	c.344G>A	p.Ser115Asn	missense_variant	4/4	1	NM_138439.3	ENSP00000380159.3	Q96CP2
FLYWCH2	ENST00000293981.10 linkuse as main transcript	c.344G>A	p.Ser115Asn	missense_variant	4/4	3		ENSP00000293981.6	Q96CP2
FLYWCH2	ENST00000572786.1 linkuse as main transcript	n.226G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000719

AC:

AN:

250176

Hom.:

AF XY:

0.0000443

AC XY:

AN XY:

135340

show subpopulations

Gnomad AFR exome

AF:

0.000617

Gnomad AMR exome

AF:

0.0000290

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:

0.0000177

Gnomad OTH exome

AF:

0.000820

GnomAD4 exome

AF:

0.0000274

AC:

AN:

1461494

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727058

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000217

AC:

AN:

152294

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000280

Hom.:

Bravo

AF:

0.000196

ESP6500AA

AF:

0.000682

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000906

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

Dec 17, 2023

The c.344G>A (p.S115N) alteration is located in exon 4 (coding exon 2) of the FLYWCH2 gene. This alteration results from a G to A substitution at nucleotide position 344, causing the serine (S) at amino acid position 115 to be replaced by an asparagine (N). 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

0.087

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.4

DANN

Benign

0.45

DEOGEN2

Benign

0.0039

T;T

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.26

.;T

M_CAP

Benign

0.0013

MetaRNN

Benign

0.0097

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.099

Sift

Benign

0.49

T;T

Sift4G

Benign

0.85

T;T

Polyphen

0.0

B;B

Vest4

0.048

MVP

0.10

MPC

0.13

ClinPred

0.017

GERP RS

-2.3

Varity_R

0.062

gMVP

0.043

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