Genetic Variant NM_021192.3:c.235G>A (chr2-176107590-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_021192.3(HOXD11):c.235G>A(p.Gly79Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000182 in 1,375,634 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

HOXD11
NM_021192.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.21

Variant links:

Genes affected

HOXD11 (HGNC:5134): (homeobox D11) This gene belongs to the homeobox family of genes. The homeobox genes encode a highly conserved family of transcription factors that play an important role in morphogenesis in all multicellular organisms. Mammals possess four similar homeobox gene clusters, HOXA, HOXB, HOXC and HOXD, located on different chromosomes, consisting of 9 to 11 genes arranged in tandem. This gene is one of several homeobox HOXD genes located in a cluster on chromosome 2. Deletions that remove the entire HOXD gene cluster or the 5' end of this cluster have been associated with severe limb and genital abnormalities. The product of the mouse Hoxd11 gene plays a role in forelimb morphogenesis. [provided by RefSeq, Jul 2008]

HOXD11 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 22 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
HOXD11	NM_021192.3 link	c.235G>A	p.Gly79Ser	missense_variant	Exon 1 of 2	ENST00000249504.7	NP_067015.2	P31277
HOXD11	XR_007073114.1 link	n.311G>A		non_coding_transcript_exon_variant	Exon 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
HOXD11	ENST00000249504.7 link	c.235G>A	p.Gly79Ser	missense_variant	Exon 1 of 2	3	NM_021192.3	ENSP00000249504.5		P31277
HOXD11	ENST00000498438.1 link	n.412-1317G>A		intron_variant	Intron 1 of 1	1

Frequencies

GnomAD3 genomes

AF:

0.0000202

AC:

AN:

148578

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000449

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000179

AC:

AN:

1227056

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

598054

show subpopulations

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:

0.0000203

Gnomad4 OTH exome

AF:

0.0000409

GnomAD4 genome

AF:

0.0000202

AC:

AN:

148578

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72464

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000449

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000912

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.073

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.47

FATHMM_MKL

Benign

0.52

LIST_S2

Benign

0.50

M_CAP

Pathogenic

0.78

MetaRNN

Uncertain

0.44

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.1

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.72

REVEL

Uncertain

0.30

Sift

Benign

0.18

Sift4G

Benign

0.43

Polyphen

0.99

Vest4

0.41

MutPred

0.28

Gain of glycosylation at G79 (P = 0);

MVP

0.83

ClinPred

0.14

GERP RS

1.3

Varity_R

0.10

gMVP

0.40

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over