Genetic Variant GRAMD2B:p.Lys82Lys (chr5-126469719-G-A) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP7

The NM_023927.4(GRAMD2B):c.246G>A(p.Lys82Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000376 in 1,597,246 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

GRAMD2B
NM_023927.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.30

Publications

0 publications found

Variant links:

Genes affected

GRAMD2B (HGNC:24911): (GRAM domain containing 2B) Enables identical protein binding activity. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

GRAMD2B links:

ENSG00000250602 (HGNC:):

ENSG00000250602 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.32).

BP7

Synonymous conserved (PhyloP=1.3 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_023927.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRAMD2B	NM_023927.4	MANE Select	c.246G>A	p.Lys82Lys	synonymous	Exon 3 of 14	NP_076416.2	Q96HH9-1
GRAMD2B	NM_001146319.3		c.291G>A	p.Lys97Lys	synonymous	Exon 3 of 14	NP_001139791.1	Q96HH9-3
GRAMD2B	NM_001349544.2		c.270G>A	p.Lys90Lys	synonymous	Exon 4 of 15	NP_001336473.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRAMD2B	ENST00000285689.8	TSL:1 MANE Select	c.246G>A	p.Lys82Lys	synonymous	Exon 3 of 14	ENSP00000285689.3	Q96HH9-1
GRAMD2B	ENST00000921003.1		c.246G>A	p.Lys82Lys	synonymous	Exon 3 of 15	ENSP00000591062.1
GRAMD2B	ENST00000513040.5	TSL:2	c.291G>A	p.Lys97Lys	synonymous	Exon 3 of 14	ENSP00000426120.1	Q96HH9-3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151838

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1445408

Hom.:

Cov.:

AF XY:

0.00000278

AC XY:

AN XY:

719578

show subpopulations

African (AFR)

AF:

0.0000607

AC:

AN:

32948

American (AMR)

AF:

0.00

AC:

AN:

44364

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25468

East Asian (EAS)

AF:

0.00

AC:

AN:

38618

South Asian (SAS)

AF:

0.00

AC:

AN:

86046

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50536

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5702

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1102494

Other (OTH)

AF:

0.0000338

AC:

AN:

59232

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151838

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74162

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5122

South Asian (SAS)

AF:

0.00

AC:

AN:

4742

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10594

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67958

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.32

CADD

Benign

8.6

(source)

DANN

Benign

0.84

PhyloP100

1.3

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over