Variant 1-152351174-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001014342.3(FLG2):c.6612C>T(p.Ala2204=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000373 in 1,612,810 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 2 hom. )

Consequence

FLG2
NM_001014342.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.71

Variant links:

Genes affected

FLG2 (HGNC:33276): (filaggrin 2) The filaggrin-like protein encoded by this gene is upregulated by calcium, proteolyzed by calpain 1, and is involved in epithelial homeostasis. The encoded protein is required for proper cornification in skin, with defects in this gene being associated with skin diseases. This protein also has a function in skin barrier protection. In fact, in addition to providing a physical barrier, C-terminal fragments of this protein display antimicrobial activity against P. aeruginosa and E. coli. [provided by RefSeq, Jul 2020]

FLG2 links:

FLG-AS1 (HGNC:27913): (cervical cancer associated DHX9 suppressive transcript)

FLG-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

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

BP6

Variant 1-152351174-G-A is Benign according to our data. Variant chr1-152351174-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2578581.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.71 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FLG2	NM_001014342.3 linkuse as main transcript	c.6612C>T	p.Ala2204=	synonymous_variant	3/3	ENST00000388718.5
FLG-AS1	NR_103778.1 linkuse as main transcript	n.1406+9964G>A		intron_variant, non_coding_transcript_variant
FLG-AS1	NR_103779.1 linkuse as main transcript	n.151+9964G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FLG2	ENST00000388718.5 linkuse as main transcript	c.6612C>T	p.Ala2204=	synonymous_variant	3/3	5	NM_001014342.3	P1
FLG-AS1	ENST00000653548.1 linkuse as main transcript	n.757+13085G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000464

AC:

AN:

150810

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000672

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000915

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000386

AC:

AN:

251172

Hom.:

AF XY:

0.000383

AC XY:

AN XY:

135728

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000879

Gnomad NFE exome

AF:

0.000652

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000364

AC:

532

AN:

1461882

Hom.:

Cov.:

AF XY:

0.000369

AC XY:

268

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00112

Gnomad4 NFE exome

AF:

0.000408

Gnomad4 OTH exome

AF:

0.000199

GnomAD4 genome

AF:

0.000464

AC:

AN:

150928

Hom.:

Cov.:

AF XY:

0.000421

AC XY:

AN XY:

73708

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000658

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000672

Gnomad4 NFE

AF:

0.000916

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000549

Hom.:

Bravo

AF:

0.000340

EpiCase

AF:

0.000491

EpiControl

AF:

0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

FLG2: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.5

DANN

Benign

0.40

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