2-10047747-A-G

Variant names:

• chr2-10047747-A-G
• rs145933214
• NM_003597.5:c.410A>G

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_003597.5(KLF11):​c.410A>G​(p.Asp137Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,613,718 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0030 (5 hom., cov: 33)
  • Exomes 𝑓: 0.00031 (2 hom.)
• Consequence: KLF11 NM_003597.5 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.30
• Publications: 5 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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0035626292).
• BP6: Variant 2-10047747-A-G is Benign according to our data. Variant chr2-10047747-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 456 AD gene.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	NM_003597.5	MANE Select	c.410A>G	p.Asp137Gly	missense	Exon 3 of 4	NP_003588.1
	KLF11	NM_001177716.2		c.359A>G	p.Asp120Gly	missense	Exon 3 of 4	NP_001171187.1
	KLF11	NM_001177718.2		c.359A>G	p.Asp120Gly	missense	Exon 3 of 4	NP_001171189.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF11	ENST00000305883.6	TSL:1 MANE Select	c.410A>G	p.Asp137Gly	missense	Exon 3 of 4	ENSP00000307023.1
	KLF11	ENST00000535335.1	TSL:2	c.359A>G	p.Asp120Gly	missense	Exon 3 of 4	ENSP00000442722.1
	KLF11	ENST00000540845.5	TSL:2	c.359A>G	p.Asp120Gly	missense	Exon 3 of 4	ENSP00000444690.1

Frequencies

GnomAD3 genomes AF: 0.00298 AC: 454 AN: 152110 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0107

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

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: 0.0000147

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000753 AC: 189 AN: 251138 AF XY: 0.000552

Gnomad AFR exome AF: 0.0102

Gnomad AMR exome AF: 0.000521

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000310 AC: 453 AN: 1461488 Hom.: 2 Cov.: 37 AF XY: 0.000293 AC XY: 213 AN XY: 727080

African (AFR) AF: 0.0102 AC: 340 AN: 33480

American (AMR) AF: 0.000581 AC: 26 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53032

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000414 AC: 46 AN: 1112004

Other (OTH) AF: 0.000629 AC: 38 AN: 60388

GnomAD4 genome AF: 0.00300 AC: 456 AN: 152230 Hom.: 5 Cov.: 33 AF XY: 0.00324 AC XY: 241 AN XY: 74436

African (AFR) AF: 0.0107 AC: 445 AN: 41524

American (AMR) AF: 0.000458 AC: 7 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68018

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000971 Hom.: 1

Bravo AF: 0.00316

ESP6500AA AF: 0.00999 AC: 44

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000939 AC: 114

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Jun 22, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

Sep 05, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Monogenic diabetes Benign:1

Jun 26, 2017

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria:BP4 (9 predictors), BS2 (24 cases and 17 controls in type2diabetesgenetics.org), BS1 (1.21% 1000G African)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	9.8
DANN	Benign	0.41
DEOGEN2	Benign	0.055	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.31	N
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.0036	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N
PhyloP100		1.3
PrimateAI	Benign	0.33	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.055
Sift	Benign	0.61	T
Sift4G	Benign	0.62	T
Polyphen		0.0090	B
Vest4		0.13
MVP		0.48
MPC		0.023
ClinPred		0.0013	T
GERP RS		3.1
Varity_R		0.041
gMVP		0.16
Mutation Taster		=97/3	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs145933214; hg19: chr2-10187874; COSMIC: COSV99045382;