X-21856280-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_206923.4(YY2):c.-205C>G variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., 1 hem., cov: 17)

Exomes 𝑓: 0.000019 ( 0 hom. 2 hem. )

Failed GnomAD Quality Control

Consequence

YY2
NM_206923.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.227

Publications

0 publications found

Variant links:

Genes affected

YY2 (HGNC:31684): (YY2 transcription factor) The protein encoded by this gene is a transcription factor that includes several Kruppel-like zinc fingers in its C-terminal region. It possesses both activation and repression domains, and it can therefore have both positive and negative effects on the transcription of target genes. This gene has an intronless coding region, and it appears to have arisen by retrotransposition of the related YY1 transcription factor gene, which is located on chromosome 14. [provided by RefSeq, May 2010]

YY2 links:

MBTPS2 (HGNC:15455): (membrane bound transcription factor peptidase, site 2) This gene encodes a intramembrane zinc metalloprotease, which is essential in development. This protease functions in the signal protein activation involved in sterol control of transcription and the ER stress response. Mutations in this gene have been associated with ichthyosis follicularis with atrichia and photophobia (IFAP syndrome); IFAP syndrome has been quantitatively linked to a reduction in cholesterol homeostasis and ER stress response.[provided by RefSeq, Aug 2009]

MBTPS2 Gene-Disease associations (from GenCC):

IFAP syndrome 1, with or without BRESHECK syndrome
Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, Ambry Genetics
keratosis follicularis spinulosa decalvans
Inheritance: XL, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: G2P, Orphanet
Olmsted syndrome, X-linked
Inheritance: XL Classification: STRONG, LIMITED Submitted by: G2P, Ambry Genetics
osteogenesis imperfecta, type 19
Inheritance: XL Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
mutilating palmoplantar keratoderma with periorificial keratotic plaques
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
osteogenesis imperfecta
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
BRESEK syndrome
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet
keratosis follicularis spinulosa decalvans, X-linked
Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

MBTPS2 links:

ENSG00000308122 (HGNC:):

ENSG00000308122 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BS2

High Hemizygotes in GnomAdExome4 at 2 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_206923.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YY2	NM_206923.4	MANE Select	c.-205C>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	NP_996806.2	O15391
YY2	NM_206923.4	MANE Select	c.-205C>G	5_prime_UTR	Exon 1 of 1	NP_996806.2	O15391
MBTPS2	NM_015884.4	MANE Select	c.670+2777C>G	intron	N/A	NP_056968.1	O43462

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
YY2	ENST00000429584.3	TSL:6 MANE Select	c.-205C>G	5_prime_UTR_premature_start_codon_gain	Exon 1 of 1	ENSP00000389381.2	O15391
YY2	ENST00000429584.3	TSL:6 MANE Select	c.-205C>G	5_prime_UTR	Exon 1 of 1	ENSP00000389381.2	O15391
MBTPS2	ENST00000379484.10	TSL:1 MANE Select	c.670+2777C>G	intron	N/A	ENSP00000368798.5	O43462

Frequencies

GnomAD3 genomes

AF:

0.0000137

AC:

AN:

73197

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:

0.0000261

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000189

AC:

AN:

212092

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73690

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

4040

American (AMR)

AF:

0.00

AC:

AN:

7242

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

6006

East Asian (EAS)

AF:

0.00

AC:

AN:

11380

South Asian (SAS)

AF:

0.0000544

AC:

AN:

18391

European-Finnish (FIN)

AF:

0.00

AC:

AN:

13951

Middle Eastern (MID)

AF:

0.00

AC:

AN:

864

European-Non Finnish (NFE)

AF:

0.0000144

AC:

AN:

138610

Other (OTH)

AF:

0.0000861

AC:

AN:

11608

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000137

AC:

AN:

73197

Hom.:

Cov.:

AF XY:

0.0000448

AC XY:

AN XY:

22343

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

16613

American (AMR)

AF:

0.00

AC:

AN:

6512

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1901

East Asian (EAS)

AF:

0.00

AC:

AN:

2209

South Asian (SAS)

AF:

0.00

AC:

AN:

2112

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4105

Middle Eastern (MID)

AF:

0.00

AC:

AN:

171

European-Non Finnish (NFE)

AF:

0.0000261

AC:

AN:

38244

Other (OTH)

AF:

0.00

AC:

AN:

987

Age Distribution

Genome Hom

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.0000227

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.5

(source)

DANN

Benign

0.66

PhyloP100

-0.23

PromoterAI

0.11

Neutral

(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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over