7-27100618-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006735.4(HOXA2):c.*108C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,176,154 control chromosomes in the GnomAD database, including 1,280 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.033 (111 hom., cov: 33)
  • Exomes 𝑓: 0.043 (1169 hom.)
• Consequence: HOXA2 NM_006735.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.248

Genes affected

HOXA2 (HGNC:5103): (homeobox A2) 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. The encoded protein may be involved in the placement of hindbrain segments in the proper location along the anterior-posterior axis during development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 7-27100618-G-A is Benign according to our data. Variant chr7-27100618-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 359977.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
HOXA2	NM_006735.4	c.*108C>T		3_prime_UTR_variant	2/2	ENST00000222718.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
HOXA2	ENST00000222718.7	c.*108C>T		3_prime_UTR_variant	2/2	1	NM_006735.4	P1

Frequencies

GnomAD3 genomes AF: 0.0328 AC: 4989 AN: 152214 Hom.: 112 Cov.: 33

Gnomad AFR AF: 0.00902

Gnomad AMI AF: 0.0220

Gnomad AMR AF: 0.0350

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00931

Gnomad FIN AF: 0.0180

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0531

Gnomad OTH AF: 0.0402

GnomAD4 exome AF: 0.0432 AC: 44258 AN: 1023822 Hom.: 1169 Cov.: 13 AF XY: 0.0426 AC XY: 22417 AN XY: 526588

Gnomad4 AFR exome AF: 0.00840

Gnomad4 AMR exome AF: 0.0292

Gnomad4 ASJ exome AF: 0.0362

Gnomad4 EAS exome AF: 0.0000267

Gnomad4 SAS exome AF: 0.0116

Gnomad4 FIN exome AF: 0.0201

Gnomad4 NFE exome AF: 0.0526

Gnomad4 OTH exome AF: 0.0402

GnomAD4 genome AF: 0.0327 AC: 4986 AN: 152332 Hom.: 111 Cov.: 33 AF XY: 0.0309 AC XY: 2299 AN XY: 74486

Gnomad4 AFR AF: 0.00902

Gnomad4 AMR AF: 0.0350

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00931

Gnomad4 FIN AF: 0.0180

Gnomad4 NFE AF: 0.0531

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0454 Hom.: 37

Bravo AF: 0.0340

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Human HOXA1 syndromes Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bosley-Salih-Alorainy syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Bilateral microtia-deafness-cleft palate syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.8
Dann	Benign	0.63

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: rs117630421; hg19: chr7-27140237; COSMIC: COSV56065844; COSMIC: COSV56065844;