chr2-238848464-C-T

Position:

• chr2-238848464-C-T

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001271893.4(TWIST2):​c.249C>T​(p.Asn83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000283 in 1,412,472 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: TWIST2 NM_001271893.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.361

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]

ACMG classification

Verdict is Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 2-238848464-C-T is Benign according to our data. Variant chr2-238848464-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 725730.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.361 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
TWIST2	NM_001271893.4	c.249C>T	p.Asn83=	synonymous_variant	1/2	ENST00000612363.2
TWIST2	NM_057179.3	c.249C>T	p.Asn83=	synonymous_variant	1/2
TWIST2	XR_007069137.1	n.380C>T		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
TWIST2	ENST00000612363.2	c.249C>T	p.Asn83=	synonymous_variant	1/2	1	NM_001271893.4	P1
TWIST2	ENST00000448943.2	c.249C>T	p.Asn83=	synonymous_variant	1/2	1		P1
TWIST2	ENST00000710607.1	c.249C>T	p.Asn83=	synonymous_variant	1/2			P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000283 AC: 4 AN: 1412472 Hom.: 0 Cov.: 31 AF XY: 0.00000429 AC XY: 3 AN XY: 698688

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000367

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 13, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	14
DANN	Benign	0.97

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

LitVar

Other links and lift over

dbSNP: rs903088398; hg19: chr2-239757105;