rs1056169851

Variant names:

• chrX-21856280-C-G
• rs1056169851
• NM_206923.4:c.-205C>G

Your query was ambiguous. Multiple possible variants found:

• chrX-21856280-C-G
• chrX-21856280-C-A
• chrX-21856280-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.227
• Publications: 0 publications found

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]

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

ENSG00000308122 (HGNC:):

ACMG classification

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	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: 1 AN: 73197 Hom.: 0 Cov.: 17

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: 4 AN: 212092 Hom.: 0 Cov.: 3 AF XY: 0.0000271 AC XY: 2 AN XY: 73690

African (AFR) AF: 0.00 AC: 0 AN: 4040

American (AMR) AF: 0.00 AC: 0 AN: 7242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6006

East Asian (EAS) AF: 0.00 AC: 0 AN: 11380

South Asian (SAS) AF: 0.0000544 AC: 1 AN: 18391

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 13951

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 864

European-Non Finnish (NFE) AF: 0.0000144 AC: 2 AN: 138610

Other (OTH) AF: 0.0000861 AC: 1 AN: 11608

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000137 AC: 1 AN: 73197 Hom.: 0 Cov.: 17 AF XY: 0.0000448 AC XY: 1 AN XY: 22343

African (AFR) AF: 0.00 AC: 0 AN: 16613

American (AMR) AF: 0.00 AC: 0 AN: 6512

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1901

East Asian (EAS) AF: 0.00 AC: 0 AN: 2209

South Asian (SAS) AF: 0.00 AC: 0 AN: 2112

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4105

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 171

European-Non Finnish (NFE) AF: 0.0000261 AC: 1 AN: 38244

Other (OTH) AF: 0.00 AC: 0 AN: 987

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000227

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	1.5
DANN	Benign	0.66
PhyloP100		-0.23
PromoterAI		0.11	Neutral

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1056169851; hg19: chrX-21874398;