14-23549129-T-A

Position:

• chr14-23549129-T-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_033400.3(ZFHX2):​c.-50+2214A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 30)
• Consequence: ZFHX2 NM_033400.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

ZFHX2 (HGNC:20152): (zinc finger homeobox 2) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in regulation of sensory perception of pain. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZFHX2-AS1 (HGNC:52658): (ZFHX2 antisense RNA 1)

THTPA (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZFHX2	NM_033400.3	c.-50+2214A>T		intron_variant		ENST00000419474.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZFHX2	ENST00000419474.5	c.-50+2214A>T		intron_variant		5	NM_033400.3	P1
ZFHX2-AS1	ENST00000553985.1	n.239-9566T>A		intron_variant, non_coding_transcript_variant		2
ZFHX2	ENST00000412565.2	c.-50+6594A>T		intron_variant		2
ZFHX2-AS1	ENST00000556354.5	n.466-9566T>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.70
DANN	Benign	0.77

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: rs222682; hg19: chr14-24018338;