rs387906973

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP2

The NM_001271893.4(TWIST2):c.355C>G(p.Gln119Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,430,430 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q119R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

TWIST2
NM_001271893.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Publications

0 publications found

Variant links:

Genes affected

TWIST2 (HGNC:20670): (twist family bHLH transcription factor 2) The protein encoded by this gene is a basic helix-loop-helix type transcription factor and shares similarity with Twist. This protein may inhibit osteoblast maturation and maintain cells in a preosteoblast phenotype during osteoblast development. This gene may be upregulated in certain cancers. Mutations in this gene cause focal facial dermal dysplasia 3, Setleis type. Two transcript variants encoding the same protein have been found. [provided by RefSeq, Apr 2014]

TWIST2 Gene-Disease associations (from GenCC):

ablepharon macrostomia syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae)
Barber-Say syndrome
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
focal facial dermal dysplasia type III
Inheritance: AD, AR Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), G2P

TWIST2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 3 curated pathogenic missense variants (we use a threshold of 10). The gene has 0 curated benign missense variants. Gene score misZ: 2.1324 (below the threshold of 3.09). Trascript score misZ: 0.22546 (below the threshold of 3.09). GenCC associations: The gene is linked to ablepharon macrostomia syndrome, focal facial dermal dysplasia type III, Barber-Say syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TWIST2	NM_001271893.4 link	c.355C>G	p.Gln119Glu	missense_variant	Exon 1 of 2	ENST00000612363.2	NP_001258822.1	Q8WVJ9A1MB48
TWIST2	NM_057179.3 link	c.355C>G	p.Gln119Glu	missense_variant	Exon 1 of 2		NP_476527.1	Q8WVJ9A1MB48
TWIST2	XR_007069137.1 link	n.486C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
TWIST2	ENST00000612363.2 link	c.355C>G	p.Gln119Glu	missense_variant	Exon 1 of 2	1	NM_001271893.4	ENSP00000482581.1	Q8WVJ9
TWIST2	ENST00000448943.2 link	c.355C>G	p.Gln119Glu	missense_variant	Exon 1 of 2	1		ENSP00000405176.2	Q8WVJ9
TWIST2	ENST00000710607.1 link	c.355C>G	p.Gln119Glu	missense_variant	Exon 1 of 2			ENSP00000518373.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.99e-7

AC:

AN:

1430430

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

709084

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32744

American (AMR)

AF:

0.00

AC:

AN:

41176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25656

East Asian (EAS)

AF:

0.00

AC:

AN:

38220

South Asian (SAS)

AF:

0.00

AC:

AN:

81996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45758

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5746

European-Non Finnish (NFE)

AF:

9.09e-7

AC:

AN:

1099650

Other (OTH)

AF:

0.00

AC:

AN:

59484

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Pathogenic

0.23

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.97

DEOGEN2

Uncertain

0.45

T;T

Eigen

Benign

0.11

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

.;D

M_CAP

Pathogenic

0.46

MetaRNN

Uncertain

0.49

T;T

MetaSVM

Pathogenic

0.94

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

7.6

PrimateAI

Uncertain

0.77

PROVEAN

Uncertain

-2.7

D;.

REVEL

Uncertain

0.60

Sift

Benign

0.12

T;.

Sift4G

Benign

0.17

T;T

Polyphen

0.096

B;B

Vest4

0.66

MutPred

0.30

Gain of disorder (P = 0.1735);Gain of disorder (P = 0.1735);

MVP

0.97

MPC

1.7

ClinPred

0.79

GERP RS

5.0

PromoterAI

0.0060

Neutral

(source)

Varity_R

0.55

gMVP

0.92

Mutation Taster

=57/43

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over