Variant 7-27199462-A-AGGC details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_000522.5(HOXA13):c.615_616insGCC(p.Ala205dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00044 in 1,612,492 control chromosomes in the GnomAD database, including 2 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00045 ( 2 hom. )

Consequence

HOXA13
NM_000522.5 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.01

Variant links:

Genes affected

HOXA13 (HGNC:5102): (homeobox A13) In vertebrates, the genes encoding the class of transcription factors called homeobox genes are found in clusters named A, B, C, and D on four separate chromosomes. Expression of these proteins is spatially and temporally regulated during embryonic development. This gene is part of the A cluster on chromosome 7 and encodes a DNA-binding transcription factor which may regulate gene expression, morphogenesis, and differentiation. Expansion of a polyalanine tract in the encoded protein can cause hand-foot-uterus syndrome, also known as hand-foot-genital syndrome. [provided by RefSeq, Jul 2008]

HOXA13 links:

HOTTIP (HGNC:37461): (HOXA distal transcript antisense RNA) This gene produces a long RNA in antisense to the HOXA gene cluster. This transcript may regulate expression of HOXA genes in cis. This gene is upregulated in tumors and is implicated in the promotion of cell proliferation. [provided by RefSeq, Dec 2017]

HOTTIP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_000522.5

BP6

Variant 7-27199462-A-AGGC is Benign according to our data. Variant chr7-27199462-A-AGGC is described in ClinVar as [Likely_benign]. Clinvar id is 2052430.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 59 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
HOXA13	NM_000522.5 linkuse as main transcript	c.615_616insGCC	p.Ala205dup	inframe_insertion	1/2	ENST00000649031.1	NP_000513.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
HOXA13	ENST00000649031.1 linkuse as main transcript	c.615_616insGCC	p.Ala205dup	inframe_insertion	1/2		NM_000522.5	ENSP00000497112	P1
HOTTIP	ENST00000421733.1 linkuse as main transcript	n.167+737_167+739dup		intron_variant, non_coding_transcript_variant		5
HOTTIP	ENST00000605136.6 linkuse as main transcript	n.86+148_86+150dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000388

AC:

AN:

151906

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

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:

0.000353

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.000272

AC:

AN:

242272

Hom.:

AF XY:

0.000309

AC XY:

AN XY:

132688

show subpopulations

Gnomad AFR exome

AF:

0.000203

Gnomad AMR exome

AF:

0.000846

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000328

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000259

Gnomad OTH exome

AF:

0.000847

GnomAD4 exome

AF:

0.000446

AC:

651

AN:

1460470

Hom.:

Cov.:

AF XY:

0.000434

AC XY:

315

AN XY:

726550

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000128

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000513

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000388

AC:

AN:

152022

Hom.:

Cov.:

AF XY:

0.000484

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00164

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000353

Gnomad4 OTH

AF:

0.000476

Bravo

AF:

0.000366

EpiCase

AF:

0.000164

EpiControl

AF:

0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Sep 07, 2022

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over