rs35927125

Variant names:

• chr2-10046292-A-G
• rs35927125
• NM_003597.5:c.185A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-10046292-A-G
• chr2-10046292-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003597.5(KLF11):​c.185A>G​(p.Gln62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,614,130 control chromosomes in the GnomAD database, including 10,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.088 (712 hom., cov: 33)
  • Exomes 𝑓: 0.11 (9513 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1 B:5
• Conservation: PhyloP100: 2.09
• Publications: 37 publications found

Genes affected

KLF11 (HGNC:11811): (KLF transcription factor 11) The protein encoded by this gene is a zinc finger transcription factor that binds to SP1-like sequences in epsilon- and gamma-globin gene promoters. This binding inhibits cell growth and causes apoptosis. Defects in this gene are a cause of maturity-onset diabetes of the young type 7 (MODY7). Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

KLF11 Gene-Disease associations (from GenCC):

• maturity-onset diabetes of the young type 7

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• maturity-onset diabetes of the young

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• monogenic diabetes

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0014551878).
• BP6: Variant 2-10046292-A-G is Benign according to our data. Variant chr2-10046292-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003597.5. 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
	KLF11	NM_003597.5	MANE Select	c.185A>G	p.Gln62Arg	missense	Exon 2 of 4	NP_003588.1	O14901-1
	KLF11	NM_001177716.2		c.134A>G	p.Gln45Arg	missense	Exon 2 of 4	NP_001171187.1	O14901-2
	KLF11	NM_001177718.2		c.134A>G	p.Gln45Arg	missense	Exon 2 of 4	NP_001171189.1	O14901-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.185A>G	p.Gln62Arg	missense	Exon 2 of 4	ENSP00000307023.1	O14901-1
	KLF11	ENST00000535335.1	TSL:2	c.134A>G	p.Gln45Arg	missense	Exon 2 of 4	ENSP00000442722.1	O14901-2
	KLF11	ENST00000540845.5	TSL:2	c.134A>G	p.Gln45Arg	missense	Exon 2 of 4	ENSP00000444690.1	O14901-2

Frequencies

GnomAD3 genomes AF: 0.0877 AC: 13342 AN: 152154 Hom.: 712 Cov.: 33

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.0888

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.00115

Gnomad SAS AF: 0.0628

Gnomad FIN AF: 0.0684

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.119

Gnomad OTH AF: 0.0999

GnomAD2 exomes AF: 0.0926 AC: 23274 AN: 251402 AF XY: 0.0954

Gnomad AFR exome AF: 0.0459

Gnomad AMR exome AF: 0.0728

Gnomad ASJ exome AF: 0.145

Gnomad EAS exome AF: 0.000653

Gnomad FIN exome AF: 0.0773

Gnomad NFE exome AF: 0.123

Gnomad OTH exome AF: 0.109

GnomAD4 exome AF: 0.110 AC: 160944 AN: 1461858 Hom.: 9513 Cov.: 34 AF XY: 0.109 AC XY: 79569 AN XY: 727230

African (AFR) AF: 0.0445 AC: 1490 AN: 33480

American (AMR) AF: 0.0737 AC: 3295 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.144 AC: 3753 AN: 26136

East Asian (EAS) AF: 0.000252 AC: 10 AN: 39700

South Asian (SAS) AF: 0.0731 AC: 6309 AN: 86258

European-Finnish (FIN) AF: 0.0785 AC: 4195 AN: 53420

Middle Eastern (MID) AF: 0.142 AC: 819 AN: 5768

European-Non Finnish (NFE) AF: 0.121 AC: 134904 AN: 1111980

Other (OTH) AF: 0.102 AC: 6169 AN: 60394

GnomAD4 genome AF: 0.0876 AC: 13345 AN: 152272 Hom.: 712 Cov.: 33 AF XY: 0.0849 AC XY: 6321 AN XY: 74474

African (AFR) AF: 0.0466 AC: 1937 AN: 41554

American (AMR) AF: 0.0887 AC: 1358 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 477 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5186

South Asian (SAS) AF: 0.0624 AC: 301 AN: 4820

European-Finnish (FIN) AF: 0.0684 AC: 726 AN: 10614

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.119 AC: 8091 AN: 68006

Other (OTH) AF: 0.0993 AC: 210 AN: 2114

Alfa AF: 0.113 Hom.: 1934

Bravo AF: 0.0885

TwinsUK AF: 0.117 AC: 433

ALSPAC AF: 0.116 AC: 447

ESP6500AA AF: 0.0429 AC: 189

ESP6500EA AF: 0.121 AC: 1044

ExAC AF: 0.0926 AC: 11249

Asia WGS AF: 0.0340 AC: 119 AN: 3478

EpiCase AF: 0.131

EpiControl AF: 0.134

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Maturity-onset diabetes of the young type 7 (1)
-	-	-	Type 2 diabetes mellitus (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	16
DANN	Benign	0.97
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.48
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.44	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.1
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.069
Sift	Benign	0.23	T
Sift4G	Benign	0.11	T
Polyphen		0.0030	B
Vest4		0.077
MPC		0.022
ClinPred		0.0058	T
GERP RS		-0.46
Varity_R		0.12
gMVP		0.11
Mutation Taster		=98/2	polymorphism (auto)

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

Other links and lift over

dbSNP: rs35927125; hg19: chr2-10186419; COSMIC: COSV59940257;