NM_000423.3:c.1469+113A>G

Variant names:

• chr12-52646627-T-C
• rs2232559
• NM_000423.3:c.1469+113A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000423.3(KRT2):​c.1469+113A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.569 in 1,137,268 control chromosomes in the GnomAD database, including 187,742 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.57 (25294 hom., cov: 32)
  • Exomes 𝑓: 0.57 (162448 hom.)
• Consequence: KRT2 NM_000423.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.04
• Publications: 9 publications found

Genes affected

KRT2 (HGNC:6439): (keratin 2) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is expressed largely in the upper spinous layer of epidermal keratinocytes and mutations in this gene have been associated with bullous congenital ichthyosiform erythroderma. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

KRT2 Gene-Disease associations (from GenCC):

• superficial epidermolytic ichthyosis

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 12-52646627-T-C is Benign according to our data. Variant chr12-52646627-T-C is described in ClinVar as Benign. ClinVar VariationId is 1226120.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.863 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT2	NM_000423.3	c.1469+113A>G		intron_variant	Intron 7 of 8	ENST00000309680.4	NP_000414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT2	ENST00000309680.4	c.1469+113A>G		intron_variant	Intron 7 of 8	1	NM_000423.3	ENSP00000310861.3

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86687 AN: 151850 Hom.: 25278 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.578

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.603

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.624

Gnomad NFE AF: 0.544

Gnomad OTH AF: 0.586

GnomAD4 exome AF: 0.569 AC: 560566 AN: 985302 Hom.: 162448 AF XY: 0.570 AC XY: 288832 AN XY: 507016

African (AFR) AF: 0.590 AC: 14283 AN: 24228

American (AMR) AF: 0.619 AC: 25366 AN: 40960

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 13469 AN: 22744

East Asian (EAS) AF: 0.879 AC: 32304 AN: 36736

South Asian (SAS) AF: 0.614 AC: 46279 AN: 75422

European-Finnish (FIN) AF: 0.515 AC: 21874 AN: 42476

Middle Eastern (MID) AF: 0.617 AC: 2078 AN: 3370

European-Non Finnish (NFE) AF: 0.545 AC: 378758 AN: 694580

Other (OTH) AF: 0.584 AC: 26155 AN: 44786

GnomAD4 genome AF: 0.571 AC: 86735 AN: 151966 Hom.: 25294 Cov.: 32 AF XY: 0.574 AC XY: 42593 AN XY: 74256

African (AFR) AF: 0.585 AC: 24265 AN: 41446

American (AMR) AF: 0.578 AC: 8831 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2067 AN: 3470

East Asian (EAS) AF: 0.885 AC: 4564 AN: 5158

South Asian (SAS) AF: 0.603 AC: 2902 AN: 4814

European-Finnish (FIN) AF: 0.515 AC: 5423 AN: 10530

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.544 AC: 36967 AN: 67954

Other (OTH) AF: 0.580 AC: 1221 AN: 2104

Alfa AF: 0.558 Hom.: 76053

Bravo AF: 0.579

Asia WGS AF: 0.679 AC: 2359 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.012
DANN	Benign	0.50
PhyloP100		-2.0
Mutation Taster		=5/95	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2232559; hg19: chr12-53040411;