rs2857667

Variant names:

• chr12-52317765-G-A
• rs2857667
• NM_002282.3:c.666C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-52317765-G-A
• chr12-52317765-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_002282.3(KRT83):​c.666C>T​(p.Cys222Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,611,946 control chromosomes in the GnomAD database, including 137,887 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13481 hom., cov: 31)
  • Exomes 𝑓: 0.41 (124406 hom.)
• Consequence: KRT83 NM_002282.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.996
• Publications: 18 publications found

Genes affected

KRT83 (HGNC:6460): (keratin 83) The protein encoded by this gene is a member of the keratin gene family. As a type II hair keratin, it is a basic protein which heterodimerizes with type I keratins to form hair and nails. The type II hair keratins are clustered in a region of chromosome 12q13 and are grouped into two distinct subfamilies based on structure similarity. One subfamily, consisting of KRTHB1, KRTHB3, and KRTHB6, is highly related. The other less-related subfamily includes KRTHB2, KRTHB4, and KRTHB5. All hair keratins are expressed in the hair follicle; this hair keratin, as well as KRTHB1 and KRTHB6, is found primarily in the hair cortex. [provided by RefSeq, Jul 2008]

KRT83 Gene-Disease associations (from GenCC):

• monilethrix

  Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Orphanet
• erythrokeratodermia variabilis

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT83-AS1 (HGNC:58282):

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.51).
• BP6: Variant 12-52317765-G-A is Benign according to our data. Variant chr12-52317765-G-A is described in ClinVar as Benign. ClinVar VariationId is 309525.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.996 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002282.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT83	NM_002282.3	MANE Select	c.666C>T	p.Cys222Cys	synonymous	Exon 4 of 9	NP_002273.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT83	ENST00000293670.3	TSL:1 MANE Select	c.666C>T	p.Cys222Cys	synonymous	Exon 4 of 9	ENSP00000293670.3
	KRT83-AS1	ENST00000740301.1		n.507-4937G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.415 AC: 63084 AN: 151830 Hom.: 13460 Cov.: 31

Gnomad AFR AF: 0.485

Gnomad AMI AF: 0.593

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.396

GnomAD2 exomes AF: 0.375 AC: 94369 AN: 251448 AF XY: 0.382

Gnomad AFR exome AF: 0.488

Gnomad AMR exome AF: 0.256

Gnomad ASJ exome AF: 0.346

Gnomad EAS exome AF: 0.203

Gnomad FIN exome AF: 0.354

Gnomad NFE exome AF: 0.416

Gnomad OTH exome AF: 0.381

GnomAD4 exome AF: 0.409 AC: 596802 AN: 1459998 Hom.: 124406 Cov.: 55 AF XY: 0.409 AC XY: 297384 AN XY: 726378

African (AFR) AF: 0.490 AC: 16374 AN: 33440

American (AMR) AF: 0.269 AC: 12039 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.348 AC: 9098 AN: 26116

East Asian (EAS) AF: 0.208 AC: 8268 AN: 39694

South Asian (SAS) AF: 0.428 AC: 36898 AN: 86220

European-Finnish (FIN) AF: 0.355 AC: 18957 AN: 53416

Middle Eastern (MID) AF: 0.380 AC: 2133 AN: 5618

European-Non Finnish (NFE) AF: 0.422 AC: 468625 AN: 1110476

Other (OTH) AF: 0.405 AC: 24410 AN: 60300

GnomAD4 genome AF: 0.416 AC: 63141 AN: 151948 Hom.: 13481 Cov.: 31 AF XY: 0.411 AC XY: 30486 AN XY: 74258

African (AFR) AF: 0.486 AC: 20147 AN: 41458

American (AMR) AF: 0.348 AC: 5316 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1217 AN: 3462

East Asian (EAS) AF: 0.203 AC: 1043 AN: 5144

South Asian (SAS) AF: 0.428 AC: 2060 AN: 4810

European-Finnish (FIN) AF: 0.343 AC: 3619 AN: 10558

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28262 AN: 67922

Other (OTH) AF: 0.392 AC: 826 AN: 2108

Alfa AF: 0.311 Hom.: 1229

Bravo AF: 0.418

EpiCase AF: 0.418

EpiControl AF: 0.428

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Monilethrix (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.51
CADD	Benign	3.6
DANN	Benign	0.83
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs2857667; hg19: chr12-52711549; COSMIC: COSV53339188;